Effect And Mechanisms Of Carbon Monoxide-releasing Molecules In Monocrotaline-induced Pulmonary Hypertension In Rats

Objective:To elucidate the therapeutic effect of exogenous CO-releasing molecule(CORM-2) in the monocrotaline(MCT)-induced pulmonary arterial hypertension(PAH) rat model and possible molecular mechanisms.Methods:â‘ Established the pulmonary arterial hypertension(PAH) model,Adult male SD rats(n=50 rats),one-time injection of MCT 60mg·kg^-1.Two weeks after internal jugular vein cannulation measured right ventricular pressure was significantly increased for pulmonary hypertension model,selected the successful model of pulmonary hypertension in rats 40.â‘¡division(n=10 is only a total of 5 groups): normal group(N group);PAH model group(P group);CORM-2(4mg·kg^-1·d^-1) Group(4CGroup);CORM-2(2mg·kg^-1·d^-1) Group(2C Group); iCORM-2 group(i=inactive non-activityIC group)(the later 4 groups were randomly divided by the 40 successful model of pulmonary hypertension in rats).â‘¢detection indicators:7days later the measurement of pulmonary artery systolic pressure(mPAP) and right ventricular systolic pressure(sRVP);arterial blood gas analysis of blood oxygen pressure(PaO₂) changes;right ventricular hypertrophy index measuring right ventricular free wall weight/(left ventricular+septal) weight[RV/ (LV+VS)];wet and dry lung weight ratio;check the lung and cardiac tissue sent to pathological examination,lung tissue homogenate centrifuged measuring NOand NOS(eNOS and iNOS).Results:â‘ The body weight and the basic conditions of life:N group,P Group,IC Group,4C group,2C Group are as follows:【(316.2±3.09)g,(211.13±10.56) g,(217.67±7.01) g,(258.5±3.06) g,(239.25±5.17) g,compared with the N group,P Group,IC Group,2C group body weight decreased significantly(P＜0.01),4C group lightly loss (0.01＜P＜0.05) group,compared with the P Group,4C group,2C rats weight gain(P＜0.05),IC group has no significant(P＞0.05).4C Group, 2C rats activity increased markedly and improved cold,restaurants increased,reduce the mortality rate.â‘¡N group,P Group,IC Group,4C group,2C Group mPAP,sRVP are as follows:【(10±0.77,15±0.77) mmHg,(32.50±2.96,41.88±3.12) mmHg,(34.17±3.72,43.83±5.95)mmHg,(17.17±1.85,23.50±0.99)mmHg,(21.13±2.01,28.88±2.97)mmHg,compared with the N group,P Group,IC Group,2C group,mPAP,sRVP significantly higher(P＜0.01),4C group increased (0.01＜P＜0.05),compared with the P Group,4C group,2C Group mPAP, sRVP decreased(P＜0.05),IC Group has not changed(P＞0.05).N group, P Group,IC Group,4C group,2C Group PaO2 are:【(109.33±4.14) mmHg,(38.63±3.42) mmHg,(41.00±5.04) mmHg,(87.00±6.82) mmHg,(67.88±4.55) mmHg】,Compared with the N group,P Group,IC Group,2C group,PaO2 decreased significantly(P＜0.01),4C Group PaO2 decreased(0.010.05).N group,P Group,IC Group,4C group,2C Group RV/(LV+VS) are:【(0.23±0.01)%,(0.52±0.20)%,(0.49±0.23)%,(0.35±0.24)%,(0.41±0.25)%】, compared with the N group,P Group,IC Group,4C,2C Group RV/(LV +VS) value increased(P<0.01),compared with the P Group,4C,2C Group RV/(LV+VS) decreased significantly(P<0.05),IC group did not change(P>0.05).N group,P Group,IC Group,4C group,2C group of wet and dry lung weight ratio are:【(0.21±0.03)%,(0.25±0.09)%,(0.28±0.01)%,(0.17±0.05)%,(0.20±0.05)%】,compared with the N group, P Group,IC Group,4C,2C group of wet and dry lung weight ratio increased(P<0.01),and P group,4C,2C group of wet and dry lung weight ratio decreased significantly(P<0.05),IC Group has not changed (P>0.05).N group,P Group,IC Group,4C group,2C Group iNOS, eNOS are:【(0.13±0.01,0.37±0.02) u/mgprot,(0.45±0.02,0.18±0.01) u/mgprot,(0.44±0.02,0.20±0.02) u/mgprot,(0.13±0.03,0.32±0.02) u /mgprot,(0.22±0.03,0.31±0.02) u/mgprot,compared with the N group,P Group,IC Group,2C Group NO,eNOS decreased iNO S significantly increased(P <0.05);4C Group NO,eNOS,iNO S has been near normal (P>0.05),compared with the P Group,4C,2C group iNOS increased NO,eNOS decreased(P <0.01);IC group change was not significant (P>0.05). Conclusion:CORM-2 on MCT-induced PAH have therapeutic effects in rats,its mechanism may be the regulation of eNOS,iNOS activity,the impact of the emergence of NO-related.