phenotyping-mouse-pulmonary-function-vivo-with-lung-diffusing

Phenotyping Mouse Pulmonary Function <em>In Vivo</em> with the Lung Diffusing Capacity

The mouse is now the primary animal used to model a variety of lung diseases. To study the mechanisms that underlie such pathologies, phenotypic methods ...

measurement-of-the-pressure-volume-curve-in-mouse-lungs

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Johns Hopkins University Bloomberg School of Public Health

Johns Hopkins University

&#x80BA;&#x5B9E;&#x8D28;&#x901A;&#x5E38;&#x88AB;&#x8BA4;&#x4E3A;&#x662F;&#x5404;&#x5411;&#x540C;&#x6027;&#xFF0C;&#x5176;&#x5C5E;&#x6027;&#x5C31;&#x662F;&#x505A;&#x4E0D;&#x53D6;&#x51B3;&#x4E8E;&#x7279;&#x5B9A;&#x7684;&#x4F18;&#x5148;&#x65B9;&#x5411;&#x3002;&#x5404;&#x5411;&#x540C;&#x6027;&#x7684;&#x5047;&#x8BBE;&#x662F;&#x91CD;&#x8981;&#x7684;&#x662F;&#x8FD9;&#x4E24;&#x4E2A;&#x6A21;&#x578B;&#x7684;&#x80BA;&#x529B;&#x5B66;&#x6027;&#x80FD;&#x548C;&#x5B9A;&#x91CF;&#x7EC4;&#x7EC7;&#x5B66;&#x6D4B;&#x91CF;&#x3002;&#x8FD9;&#x79CD;&#x5047;&#x8BBE;&#xFF0C;&#x4F46;&#x662F;&#xFF0C;&#x4E0D;&#x88AB;&#x5148;&#x524D;&#x5DF2;&#x5BA1;&#x67E5;&#x5728;&#x5FAE;&#x89C2;&#x5C42;&#x9762;&#xFF0C;&#x90E8;&#x5206;&#x539F;&#x56E0;&#x662F;&#x96BE;&#x4EE5;&#x83B7;&#x5F97;&#x8DB3;&#x591F;&#x6570;&#x91CF;&#x7684;&#x7EC4;&#x7EC7;&#x5C0F;&#x6837;&#x672C;&#x540C;&#x65F6;&#x4FDD;&#x6301;&#x7A7A;&#x95F4;&#x5B9A;&#x5411;&#x7684;&#x5927;&#x578B;&#x80BA;&#x91CC;&#x3002;&#x5728;&#x9F20;&#x6807;&#xFF0C;&#x7136;&#x800C;&#xFF0C;&#x8FD9;&#x79CD;&#x56F0;&#x96BE;&#x6700;&#x5C0F;&#x5316;&#x3002;&#x6211;&#x4EEC;&#x4ECE;&#x9AD8;&#x5206;&#x8FA8;&#x7387;&#x7EC4;&#x7EC7;&#x5B66;&#x7684;&#x5B8C;&#x6574;&#x7AE0;&#x8282;&#x5305;&#x56F4;&#x5B8C;&#x6574;&#x8FDE;&#x7EED;&#x7684;&#x5185;&#x810F;&#x80F8;&#x8154;&#x819C;&#x8BA1;&#x7B97;&#x9F20;&#x6807;&#x80BA;&#x80BE;&#x5B9E;&#x8D28;&#x5404;&#x5411;&#x540C;&#x6027;&#x901A;&#x8FC7;&#x91CF;&#x5316;&#x5747;&#x503C;&#x9886;&#x7A7A;&#x5F26;&#x957F;&#x5EA6; (Lm)&#x3002;&#x6211;&#x4EEC;&#x5206;&#x6210;&#x8FD9;&#x80BA;&#x5165; 5 &#x4E2A;&#x5B64;&#x7ACB;&#x5730;&#x533A;&#xFF0C;&#x5B9A;&#x4E49;&#x7531;&#x5185;&#x810F;&#x80F8;&#x819C;&#x4E4B;&#x95F4;&#x7684;&#x8DDD;&#x79BB;&#x3002;&#x8981;&#x8FDB;&#x4E00;&#x6B65;&#x8BC4;&#x4F30;&#x5404;&#x5411;&#x540C;&#x6027;&#xFF0C;&#x6211;&#x4EEC;&#x8FD8;&#x5728;&#x5BF9;&#x8BE5;&#x8282;&#x7684;&#x65B9;&#x5411;&#xFF0C;&#x4E24;&#x4E2A;&#x6B63;&#x4EA4;&#x7A7A;&#x95F4;&#x65B9;&#x5411;&#x6D4B;&#x91CF; Lm &#x548C;&#x5404;&#x4E0D;&#x76F8;&#x540C;&#x7684;&#x793A;&#x4F8B;&#x884C;&#x95F4;&#x8DDD;&#x4ECE; 3 &#x5230; 280 microm&#x3002;&#x7ED3;&#x679C;&#x8868;&#x660E;&#xFF0C;&#x6B63;&#x5E38;&#x8001;&#x9F20;&#x7684;&#x80BA;&#x5B9E;&#x8D28;&#x5404;&#x5411;&#x5F02;&#x6027;&#x7684;&#x9192;&#x76EE;&#x7A0B;&#x5EA6;&#x3002;&#x7F51;&#x683C;&#x7EBF;&#x662F;&#x5E73;&#x884C;&#x7684;&#x7EC4;&#x7EC7;&#x7684;&#x8179;&#x4FA7;&#x80CC;&#x8F74;&#x7684; Lm &#x65F6;&#x5019;&#x5927;&#x5F97;&#x591A;&#x3002;&#x53E6;&#x5916; Lm &#x662F;&#x5C0F;&#x4E86;&#x5F88;&#x591A;&#x5728; 300 microm &#x7684;&#x5185;&#x810F;&#x80F8;&#x819C;&#x5185;&#x3002;&#x662F;&#x5426;&#x6B64;&#x5404;&#x5411;&#x5F02;&#x6027;&#x7ED3;&#x679C;&#x4ECE;&#x5185;&#x5728;&#x7684;&#x7ED3;&#x6784;&#x6027;&#x56E0;&#x7D20;&#x6216;&#x975E;&#x5747;&#x5300;&#x6536;&#x7F29;&#x671F;&#x95F4;&#x5E38;&#x89C4;&#x7EC4;&#x7EC7;&#x5904;&#x7406;&#x662F;&#x4E0D;&#x786E;&#x5B9A;&#x7684;&#x4F46;&#x89E3;&#x91CA;&#x8FDB;&#x884C;&#x9F20;&#x6807;&#x80BA;&#x7684;&#x5F62;&#x6001;&#x5B9A;&#x91CF;&#x6D4B;&#x91CF;&#x65F6;&#xFF0C;&#x5E94;&#x8003;&#x8651;&#x5B83;&#x3002;

&#x9F20;&#x6807;&#x80BA;&#x5B9E;&#x8D28;&#x7684;&#x5404;&#x5411;&#x5F02;&#x6027;&#x6027;&#x8D28;&#x3002;

Lung parenchyma is normally considered to be isotropic, that is, its properties do not depend upon specific preferential directions. The assumption of isotropy is important for both modeling of lung mechanical properties and quantitative histologic measurements. This assumption, however, has not been previously examined at the microscopic level, in part because of the difficulty in large lungs of obtaining sufficient numbers of small samples of tissue while maintaining the spatial orientation. In the mouse, however, this difficulty is minimized. We evaluated the parenchymal isotropy in mouse lungs by quantifying the mean airspace chord lengths (Lm) from high-resolution histology of complete sections surrounded by an intact continuous visceral pleural membrane. We partitioned this lung into 5 isolated regions, defined by the distance from the visceral pleura. To further evaluate the isotropy, we also measured Lm in two orthogonal spatial directions with respect to the section orientation, and varied the sample line spacing from 3 to 280 microm. Results show a striking degree of parenchymal anisotropy in normal mouse lungs. The Lm was significantly greater when grid lines were parallel to the ventral-dorsal axis of the tissue. In addition the Lm was significantly smaller within 300 microm of the visceral pleura. Whether this anisotropy results from intrinsic structural factors or from nonuniform shrinkage during conventional tissue processing is uncertain, but it should be considered when interpreting quantitative morphometric measurements made in the mouse lung.

Anisotropic nature of mouse lung parenchyma.

Parenchyme pulmonaire est normalement consid&eacute;r&eacute; comme isotrope, c&#39;est-&agrave;-dire ses propri&eacute;t&eacute;s ne d&eacute;pendent pas sur des orientations pr&eacute;f&eacute;rentielles sp&eacute;cifiques. L&#39;hypoth&egrave;se d&#39;isotropie est important pour les deux la mod&eacute;lisation des propri&eacute;t&eacute;s m&eacute;caniques du poumon et des mesures quantitatives histologiques. Cette hypoth&egrave;se, toutefois, n&#39;a pas &eacute;t&eacute; pr&eacute;c&eacute;demment examin&eacute;e au niveau microscopique, en partie en raison de la difficult&eacute; &agrave; grands poumons d&#39;obtenir un nombre suffisant de petits &eacute;chantillons de tissu tout en conservant l&#39;orientation spatiale. Cependant, chez la souris, cette difficult&eacute; est minimis&eacute;e. Nous avons &eacute;valu&eacute; l&#39;isotropie parenchymateuse dans les poumons de souris en quantifiant les longueurs de corde moyenne de l&#39;espace a&eacute;rien (Lm) de haute r&eacute;solution histologie des sections enti&egrave;res, entour&eacute; d&#39;une membrane de pl&egrave;vre visc&eacute;rale continue intacte. Nous avons partitionn&eacute; ce poumon en 5 r&eacute;gions isol&eacute;es, d&eacute;finie par la distance entre la pl&egrave;vre visc&eacute;rale. Pour continuer &agrave; &eacute;valuer l&#39;isotropie, nous avons &eacute;galement mesur&eacute; Lm dans deux directions orthogonales de spatiales en ce qui concerne l&#39;orientation de la section et variait de l&#39;espacement de ligne d&#39;&eacute;chantillon de 15 &agrave; 280 microm. R&eacute;sultats montrent un degr&eacute; remarquable de parenchymateuse anisotropie dans les poumons des souris normales. Le Lm &eacute;tait significativement plus &eacute;lev&eacute; lorsque les lignes de la grille ont &eacute;t&eacute; parall&egrave;les &agrave; l&#39;axe ventraux-dorsaux du tissu. En outre, le Lm a &eacute;t&eacute; significativement plus faible dans les 300 microm de la pl&egrave;vre visc&eacute;rale. Si cette anisotropie r&eacute;sulte de facteurs structurels intrins&egrave;ques ou de r&eacute;tr&eacute;cissement non uniforme durant le tissu conventionnel traitement est incertaine, mais il devrait &ecirc;tre examin&eacute; lors de l&#39;interpr&eacute;tation des mesures morphom&eacute;triques quantitative dans les poumons de souris.

Nature anisotrope de parenchyme pulmonaire de souris.

Parenchima polmonare &egrave; normalmente considerato isotropo, ovvero le propriet&agrave; non dipendono da specifiche direzioni preferenziali. L&#39;ipotesi di isotropia &egrave; importante per entrambi modellazione delle propriet&agrave; meccaniche del polmone e le misure quantitative istologiche. Questa ipotesi, tuttavia, non precedentemente esaminata a livello microscopico, in parte a causa della difficolt&agrave; nelle grandi polmoni di ottenere un numero sufficiente di piccoli campioni di tessuto, mantenendo l&#39;orientamento spaziale. Nel topo, tuttavia, questa difficolt&agrave; &egrave; ridotto al minimo. Abbiamo valutato l&#39;isotropia parenchimale nei polmoni del mouse da quantificare le lunghezze di corda media dello spazio aereo (Lm) da istologia ad alta risoluzione di sezioni complete circondato da una membrana pleurica viscerale continua intatta. Abbiamo diviso questo polmone in 5 regioni isolate, definita dalla distanza tra la pleura viscerale. Per valutare ulteriormente l&#39;isotropia, abbiamo anche misurato Lm in due direzioni ortogonali spaziale per quanto riguarda l&#39;orientamento della sezione e variato la spaziatura di linea campione da 3 microm 280. Risultati mostrano un notevole grado di anisotropia parenchimale nel polmone normale mouse. Il Lm &egrave; stato significativamente maggiore quando le linee della griglia sono parallele all&#39;asse dorso-ventrale del tessuto. Inoltre il Lm era significativamente pi&ugrave; piccolo all&#39;interno di 300 microm della pleura viscerale. Se questa anisotropia deriva da fattori strutturali intrinseche o dal ritiro non uniforme durante il tessuto tradizionale elaborazione &egrave; incerta, ma dovrebbe essere considerato quando si interpretano morfometrici quantitativi misurazioni effettuate nel polmone del mouse.

Anisotropica natura del parenchima polmonare del mouse.

&#x80BA;&#x5B9F;&#x8CEA;&#x306F;&#x901A;&#x5E38;&#x306F;&#x7B49;&#x65B9;&#x6027;&#x3068;&#x898B;&#x306A;&#x3055;&#x308C;&#x307E;&#x3059;&#x3001;&#x3064;&#x307E;&#x308A;&#x3001;&#x305D;&#x306E;&#x30D7;&#x30ED;&#x30D1;&#x30C6;&#x30A3;&#x306B;&#x7279;&#x5B9A;&#x306E;&#x512A;&#x5148;&#x65B9;&#x5411;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x307E;&#x305B;&#x3093;&#x3002;&#x7570;&#x65B9;&#x6027;&#x306E;&#x4EEE;&#x5B9A;&#x306F;&#x3001;&#x4E21;&#x65B9;&#x306E;&#x80BA;&#x306E;&#x529B;&#x5B66;&#x7279;&#x6027;&#x3068;&#x7D44;&#x7E54;&#x5B66;&#x7684;&#x5B9A;&#x91CF;&#x30E2;&#x30C7;&#x30EB;&#x5316;&#x304C;&#x91CD;&#x8981;&#x3067;&#x3059;&#x3002;&#x3053;&#x306E;&#x4EEE;&#x5B9A;&#x305F;&#x3060;&#x3057;&#x3001;&#x4EE5;&#x524D;&#x9855;&#x5FAE;&#x93E1;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x3067;&#x306F;&#x3001;&#x4E00;&#x90E8;&#x306E;&#x7A7A;&#x9593;&#x7684;&#x306A;&#x30AA;&#x30EA;&#x30A8;&#x30F3;&#x30C6;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x3092;&#x7DAD;&#x6301;&#x3057;&#x306A;&#x304C;&#x3089;&#x7D44;&#x7E54;&#x306E;&#x5C0F;&#x3055;&#x306A;&#x30B5;&#x30F3;&#x30D7;&#x30EB;&#x306E;&#x5341;&#x5206;&#x306A;&#x6570;&#x3092;&#x5F97;&#x308B;&#x5927;&#x898F;&#x6A21;&#x306A;&#x80BA;&#x306E;&#x96E3;&#x3057;&#x3055;&#x306E;&#x305F;&#x3081;&#x691C;&#x8A0E;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x3002;&#x30DE;&#x30A6;&#x30B9;&#x3067;&#x306F;&#x3001;&#x305F;&#x3060;&#x3057;&#x3001;&#x3053;&#x306E;&#x554F;&#x984C;&#x6700;&#x5C0F;&#x5316;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005; &#x306E;&#x30DE;&#x30A6;&#x30B9;&#x80BA;&#x5B9F;&#x8CEA;&#x306E;&#x7570;&#x65B9;&#x6027;&#x5E73;&#x5747;&#x7A7A;&#x57DF;&#x5F26;&#x9577; (Lm) &#x3092;&#x5B9A;&#x91CF;&#x5316;&#x3059;&#x308B;&#x3053;&#x3068;&#x3001;&#x305D;&#x306E;&#x307E;&#x307E;&#x9023;&#x7D9A;&#x5185;&#x81D3;&#x80F8;&#x819C;&#x819C;&#x306B;&#x56F2;&#x307E;&#x308C;&#x3066;&#x5B8C;&#x5168;&#x306A;&#x30BB;&#x30AF;&#x30B7;&#x30E7;&#x30F3;&#x306E;&#x9AD8;&#x89E3;&#x50CF;&#x5EA6;&#x7D44;&#x7E54;&#x304B;&#x3089;&#x8A55;&#x4FA1;&#x3002;&#x81D3;&#x5074;&#x80F8;&#x819C;&#x304B;&#x3089;&#x306E;&#x8DDD;&#x96E2;&#x306B;&#x3088;&#x3063;&#x3066;&#x5B9A;&#x7FA9;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B; 5 &#x3064;&#x306E;&#x5B64;&#x7ACB;&#x3057;&#x305F;&#x5730;&#x57DF;&#x306B;&#x3053;&#x306E;&#x80BA;&#x30D1;&#x30FC;&#x30C6;&#x30A3;&#x30B7;&#x30E7;&#x30F3;&#x5206;&#x5272;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x7570;&#x65B9;&#x6027;&#x3092;&#x8A55;&#x4FA1;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;&#x307E;&#x305F; 2 &#x3064;&#x306E;&#x76F4;&#x4EA4;&#x7A7A;&#x9593;&#x65B9;&#x5411;&#x3067;&#x30BB;&#x30AF;&#x30B7;&#x30E7;&#x30F3;&#x306E;&#x5411;&#x304D;&#x306B;&#x95A2;&#x3057;&#x3066; Lm &#x3092;&#x6E2C;&#x5B9A;&#x3057;&#x3001;3 &#x304B;&#x3089;&#x306E;&#x30B5;&#x30F3;&#x30D7;&#x30EB;&#x884C;&#x9593;&#x9694; 280 microm &#x306B;&#x69D8;&#x3005; &#x306A;&#x3002;&#x7D50;&#x679C;&#x306F;&#x901A;&#x5E38;&#x306E;&#x30DE;&#x30A6;&#x30B9;&#x80BA;&#x306E;&#x5B9F;&#x8CEA;&#x7570;&#x65B9;&#x6027;&#x306E;&#x9855;&#x8457;&#x3067;&#x3042;&#x308B;&#x3092;. &#x3057;&#x307E;&#x3059;&#x3002;&#x30B0;&#x30EA;&#x30C3;&#x30C9;&#x7DDA;&#x306F;&#x3001;&#x7D44;&#x7E54;&#x306E;&#x80CC;&#x8179;&#x8EF8;&#x306B;&#x5E73;&#x884C;&#x3057;&#x305F;&#x3068;&#x304D;&#x3001;Lm &#x306F;&#x6709;&#x610F;&#x306B;&#x5927;&#x304D;&#x304B;&#x3063;&#x305F;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;Lm &#x5927;&#x5E45;&#x306B;&#x81D3;&#x5074;&#x80F8;&#x819C;&#x306E; 300 microm &#x5185;&#x5C0F;&#x3055;&#x304B;&#x3063;&#x305F;&#x3002;&#x3053;&#x306E;&#x7570;&#x65B9;&#x6027;&#x306E;&#x4E0D;&#x5747;&#x4E00;&#x53CE;&#x7E2E;&#x304B;&#x3089;&#x3001;&#x307E;&#x305F;&#x306F;&#x672C;&#x8CEA;&#x7684;&#x306A;&#x69CB;&#x9020;&#x7684;&#x306A;&#x8981;&#x56E0;&#x304B;&#x3089;&#x7D50;&#x679C;&#x304B;&#x3069;&#x3046;&#x304B;&#x5F93;&#x6765;&#x306E;&#x7D44;&#x7E54;&#x4E2D;&#x306B;&#x51E6;&#x7406;&#x304C;&#x3001;&#x3067;&#x3059;&#x304C;&#x3001;&#x30DE;&#x30A6;&#x30B9;&#x80BA;&#x306E;&#x5B9A;&#x91CF;&#x7684;&#x5F62;&#x614B;&#x8A08;&#x6E2C;&#x5B66;&#x7684;&#x6E2C;&#x5B9A;&#x3092;&#x89E3;&#x91C8;&#x3059;&#x308B;&#x3068;&#x304D;&#x8003;&#x616E;&#x3055;&#x308C;&#x308B;&#x5FC5;&#x8981;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;

&#x30DE;&#x30A6;&#x30B9;&#x80BA;&#x5B9F;&#x8CEA;&#x306E;&#x7570;&#x65B9;&#x6027;&#x3002;

&#xD3D0; &#xC2E4;&#xC9C8;&#xC740; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xB4F1;&#xBC29;&#xC131;&#xC73C;&#xB85C; &#xAC04;&#xC8FC; &#xB429;&#xB2C8;&#xB2E4;, &#xC989;, &#xC18D;&#xC131; &#xD2B9;&#xC815; &#xC6B0;&#xC120; &#xBC29;&#xD5A5;&#xC5D0; &#xC758;&#xC874; &#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;. Isotropy &#xAC00;&#xC815; &#xBAA8;&#xB450; &#xBAA8;&#xB378;&#xB9C1; &#xD3D0; &#xAE30;&#xACC4;&#xC801; &#xC131;&#xC9C8; &#xBC0F; &#xC815;&#xB7C9; &#xC870;&#xC9C1;&#xD559; &#xCE21;&#xC815;&#xC744; &#xC704;&#xD574; &#xC911;&#xC694; &#xD558;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098;&#xC774; &#xAC00;&#xC815;,, &#xD558;&#xC9C0; &#xC774;&#xC804; &#xAC80;&#xC0AC; &#xD604;&#xBBF8;&#xACBD; &#xC218;&#xC900;&#xC5D0;&#xC11C; &#xC77C;&#xBD80; &#xD070; &#xD3D0; &#xACF5;&#xAC04; &#xC624;&#xB9AC;&#xC5D4;&#xD14C;&#xC774;&#xC158;&#xC744; &#xC720;&#xC9C0; &#xD558;&#xBA74;&#xC11C; &#xC870;&#xC9C1;&#xC758; &#xC791;&#xC740; &#xC0D8;&#xD50C;&#xC758; &#xCDA9;&#xBD84; &#xD55C; &#xC22B;&#xC790;&#xB97C; &#xC5BB;&#xAE30;&#xC758; &#xC5B4;&#xB824;&#xC6C0; &#xB54C;&#xBB38;&#xC5D0;. &#xADF8;&#xB7EC;&#xB098; &#xB9C8;&#xC6B0;&#xC2A4;,,&#xC774; &#xC5B4;&#xB824;&#xC6C0;&#xC740; &#xCD5C;&#xC18C;&#xD654; &#xB429;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xADF8;&#xB300;&#xB85C; &#xC5F0;&#xC18D; &#xB0B4;&#xC7A5; &#xB291; &#xB9C9;&#xC73C;&#xB85C; &#xB458;&#xB7EC;&#xC2F8;&#xC778; &#xC804;&#xCCB4; &#xC139;&#xC158;&#xC758; &#xACE0;&#xD574;&#xC0C1;&#xB3C4; &#xC870;&#xC9C1;&#xD559;&#xC5D0;&#xC11C; &#xC758;&#xBBF8; &#xC601;&#xACF5; &#xD654;&#xC74C; &#xAE38;&#xC774; (Lm)&#xC744; &#xCE21;&#xC815; &#xD558; &#xC5EC; &#xB9C8;&#xC6B0;&#xC2A4; &#xD3D0;&#xC5D0;&#xC11C; parenchymal isotropy &#xD3C9;&#xAC00;. &#xC6B0;&#xB9AC; &#xB0B4;&#xC7A5; &#xB291; &#xB9C9;&#xC5D0;&#xC11C; &#xAC70;&#xB9AC;&#xC5D0;&#xC11C; &#xC815;&#xC758;&#xD55C; 5 &#xACE0;&#xB9BD; &#xB41C; &#xC9C0;&#xC5ED;&#xC73C;&#xB85C;&#xC774; &#xD3D0;&#xB97C; &#xBD84;&#xD560; &#xD569;&#xB2C8;&#xB2E4;. &#xB354;&#xB294; isotropy &#xD3C9;&#xAC00;, &#xD558; &#xC6B0;&#xB9AC; Lm &#xC139;&#xC158; &#xBC29;&#xD5A5;&#xC5D0; &#xAD00;&#xD558;&#xC5EC; 2 &#xAC1C;&#xC758; &#xC9C1;&#xAD50; &#xACF5;&#xAC04; &#xBC29;&#xD5A5; &#xCE21;&#xC815; &#xBC0F; 280 microm 3&#xC5D0;&#xC11C; &#xC0D8;&#xD50C; &#xC904; &#xAC04;&#xACA9;&#xC744; &#xB2E4;&#xC591; &#xD55C;. &#xACB0;&#xACFC; &#xC815;&#xC0C1;&#xC801;&#xC778; &#xB9C8;&#xC6B0;&#xC2A4; &#xD3D0;&#xC5D0;&#xC11C; parenchymal &#xC774;&#xBC29;&#xC131;&#xC758; &#xB208;&#xC5D0; &#xB744;&#xB294; &#xC815;&#xB3C4; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xB54C; &#xB208;&#xAE08;&#xC120; &#xC870;&#xC9C1;&#xC758; &#xBCF5; &#xBD80; &#xB4F1; &#xCABD; &#xCD95;&#xC5D0; &#xD3C9;&#xD589;&#xB294; Lm &#xC0C1;&#xB2F9;&#xD788; &#xCEF8;&#xB2E4;. &#xB610;&#xD55C;&#xB294; Lm&#xC740; &#xB0B4;&#xC7A5; &#xB291; &#xB9C9;&#xC758; 300 microm&#xC5D0;&#xC11C; &#xD604;&#xC800; &#xD558; &#xAC8C; &#xB354; &#xC791;&#xC740;. &#xC774; &#xC774;&#xBC29;&#xC131; &#xB610;&#xB294; &#xBE44;&#xADE0;&#xC77C; &#xC218;&#xCD95; &#xBCF8;&#xC9C8;&#xC801;&#xC778; &#xAD6C;&#xC870;&#xC801; &#xC694;&#xC778;&#xC5D0;&#xC11C; &#xACB0;&#xACFC; &#xC5EC;&#xBD80;&#xB97C; &#xAE30;&#xC874;&#xC758; &#xC870;&#xC9C1; &#xC911; &#xCC98;&#xB9AC;&#xB294; &#xD655;&#xC2E4; &#xD558;&#xC9C0;&#xB9CC; &#xC591;&#xC801; &#xD615;&#xD0DC;&#xD559; &#xCE21;&#xC815; &#xB9C8;&#xC6B0;&#xC2A4; &#xD3D0;&#xC5D0;&#xC11C; &#xD574;&#xC11D;&#xD560; &#xB54C; &#xACE0;&#xB824;&#xD574; &#xC57C; &#xD569;&#xB2C8;&#xB2E4;.

&#xB9C8;&#xC6B0;&#xC2A4; &#xD3D0; &#xC2E4;&#xC9C8;&#xC758; &#xC774;&#xBC29;&#xC131; &#xD2B9;&#xC131;&#xC785;&#xB2C8;&#xB2E4;.

Par&eacute;nquima pulmonar es normalmente considerado como isotr&oacute;pico, es decir, sus propiedades no dependen de direcciones preferenciales espec&iacute;ficas. La asunci&oacute;n de la isotrop&iacute;a es importante para ambos modelos de propiedades mec&aacute;nicas del pulm&oacute;n y mediciones cuantitativas histologic. Esta hip&oacute;tesis, sin embargo, no ha sido previamente examinada a nivel microsc&oacute;pico, en parte debido a la dificultad en grandes pulmones de obtener un n&uacute;mero suficiente de peque&ntilde;as muestras de tejido manteniendo la orientaci&oacute;n espacial. En el rat&oacute;n, sin embargo, esta dificultad se reduce al m&iacute;nimo. Evaluamos la isotrop&iacute;a parenquimal en pulmones de rat&oacute;n mediante la cuantificaci&oacute;n de las longitudes del acorde del espacio a&eacute;reo media (Lm) de alta resoluci&oacute;n histolog&iacute;a de secciones completas, rodeado por una membrana pleural visceral continua intacta. Reparte este pulm&oacute;n en 5 regiones aisladas, definido por la distancia de la pleura visceral. Para evaluar la isotrop&iacute;a, tambi&eacute;n medimos Lm en dos direcciones ortogonales de espaciales con respecto a la orientaci&oacute;n de la secci&oacute;n y vari&oacute; el interlineado de muestra de 3 a 280 microm. Resultados muestran un sorprendente grado de anisotrop&iacute;a parenquimal en pulmones normal del rat&oacute;n. El Lm fue significativamente mayor cuando las l&iacute;neas de cuadr&iacute;cula paralelas al eje dorsal ventral del tejido. Adem&aacute;s el Lm fue significativamente menor en microm 300 de la pleura visceral. Si esta anisotrop&iacute;a resulta de factores estructurales intr&iacute;nsecos o de contracci&oacute;n no uniforme durante el tejido convencional es incierto, pero debe considerarse al interpretar las mediciones morfom&eacute;tricas cuantitativa en el pulm&oacute;n del rat&oacute;n.

Naturaleza anisotr&oacute;pica de par&eacute;nquima pulmonar de rat&oacute;n.

Approximately 3 billion people-half the worldwide population-are exposed to extremely high concentrations of household air pollution due to the burning of biomass fuels on inefficient cookstoves, accounting for 4 million annual deaths globally. Yet, our understanding of the pulmonary responses to household air pollution exposure and the underlying molecular and cellular events is limited. The two most prevalent biomass fuels in India are wood and cow dung, and typical 24-hour mean particulate matter (PM) concentrations in homes that use these fuels are 300 to 5,000 μg/m(3). We dissected the mechanisms of pulmonary responses in mice after acute or subchronic exposure to wood or cow dung PM collected from rural Indian homes during biomass cooking. Acute exposures resulted in robust proinflammatory cytokine production, neutrophilic inflammation, airway resistance, and hyperresponsiveness, all of which were significantly higher in mice exposed to PM from cow dung. On the contrary, subchronic exposures induced eosinophilic inflammation, PM-specific antibody responses, and alveolar destruction that was highest in wood PM-exposed mice. To understand the molecular pathways that trigger biomass PM-induced inflammation, we exposed Toll-like receptor (TLR)2-, TLR3-, TLR4-, TLR5-, and IL-1R-deficient mice to PM and found that IL-1R, TLR4, and TLR2 are the predominant receptors that elicit inflammatory responses via MyD88 in mice exposed to wood or cow dung PM. In conclusion, this study demonstrates that subchronic exposure to PM collected from households burning biomass fuel elicits a persistent pulmonary inflammation largely through activation of TLR and IL-1R pathways, which could increase the risk for chronic respiratory diseases.

Source of biomass cooking fuel determines pulmonary response to household air pollution.

Cigarette smoke (CS) is the most common cause of chronic obstructive pulmonary diseases (COPD), including emphysema. CS exposure impacts all cell types within the airways and lung parenchyma, causing alveolar tissue destruction through four mechanisms: (1) oxidative stress; (2) inflammation; (3) protease-induced degradation of the extracellular matrix; and (4) enhanced alveolar epithelial and endothelial cell (EC) apoptosis. Studies in human pulmonary ECs demonstrate that macrophage migration inhibitory factor (MIF) antagonizes CS-induced apoptosis. Here, we used human microvascular ECs, an animal model of emphysema (mice challenged with chronic CS), and patient serum samples to address both the capacity of CS to alter MIF expression and the effects of MIF on disease severity. We demonstrate significantly reduced serum MIF levels in patients with COPD. In the murine model, chronic CS exposure resulted in decreased MIF mRNA and protein expression in the intact lung. MIF deficiency (Mif(-/-)) potentiated the toxicity of CS exposure in vivo via increased apoptosis of ECs, resulting in enhanced CS-induced tissue remodeling. This was linked to MIF's capacity to protect against double-stranded DNA damage and suppress p53 expression. Taken together, MIF appears to antagonize CS-induced toxicity in the lung and resultant emphysematous tissue remodeling by suppressing EC DNA damage and controlling p53-mediated apoptosis, highlighting a critical role of MIF in EC homeostasis within the lung.

Jonathan Fallica

Department of Environmental Health Sciences

Johns Hopkins University Bloomberg School of Public Health

Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

Measurement of the Pressure-volume Curve in Mouse Lungs

Jonathan Fallica

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Environmental Health Sciences

Johns Hopkins University Bloomberg School of Public Health

Phenotyping Mouse Pulmonary Function In Vivo with the Lung Diffusing Capacity

Measurement of the Pressure-volume Curve in Mouse Lungs

Department of Environmental Health Sciences