Abstract:

Objective To investigate the improvement effect of effective-compound compatibility of Bufei Yishen prescrtion（ECC-BYP Ⅲ） on pulmonary hypertension （PH） of the rats induced by smoke and bacteria， and to preliminarily elucidate its mechanism. Methods SPF SD rats were randomly divided into control group （n=9） and modeling group（n=140）.The rats in control groujp were given conventional feeding，and the rats in modeling group were given cigarette-smoke and Klebsiellabacillus （Kp） to make the PH model. Then the rats in model group were divided into model group（n=10）， low（n=9）， medium（n=10）， and high（n=10） doses （3.24， 6.48 and 12.96 mg·kg^－1·d^－1） of ECC-BYP Ⅲgroups， according to the equivalent pulmonary function of the rats among various groups.The rats in ECC-BYP Ⅲ groups were administered with different doses of ECC-BYP Ⅲ， respectively， and the rats in control and model groups were administered with same volume of solvent for 4 weeks. On the 29th day，the mean pulmonary artery pressure （mPAP）， pulmonary artery systolic pressure （PASP），pulmonary artery diastolic pressure （PADP）， and right ventricular hypertrophy index （RVHI） of the rats in various groups were measured.The lung tissues of the rats in various groups were taken out. Hematoxylin-eosin（HE）staining was used to detect the periarteriolar inflammation in lung tissue；victoria blue staining was used to detect the percentages of non-muscular， partial muscular， and muscular pulmonary arterioles in pulmonary arterioles of the rats， the percentages of wall thickness of pulmonary muscular arterioles in vessel diameter（WT%），and luminal area in pulmonary muscular arterioles （LA%）. Enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of interleukin 6 （IL-6）， tumor necrosis factor （TNF-α）， endothelin-1 （ET-1）， and protracyclin （PGI2） in lung tissue of the rats in various groups. Results Compared with control group，the mPAP， PASP， PADP of the rats in model group were increased（P<0.05 or P<0.01）， RVHI was increased（P<0.01），and there were obvious inflammatory cell infiltration around the pulmonary arterioles； the levels of TNF-α and IL-6 in lung tissue were increased（P<0.01），the percentage of muscular arteriole and WT% of pulmonary were increased and non-muscular arteriole and LA% were decreased（P<0.05 or P<0.01）， and the level of ET-1 and ET-1/PGI2 ratio in lung tissue was increased（P<0.01）. Compared with model group， the mPAP and PADP of the rats in high dose of ECC-BYP Ⅲ group were decreased（P<0.05），the inflammatory cell infiltration of the rats in medium and high doses of ECC-BYP Ⅲ groups was improved，and the levels of TNF-α， IL-6， WT%，percentage of muscular arteriole were decreased（P<0.01），and LA% was increased （P<0.01）；compared with model group，the ET-1 levels in lung tissue of the rats in medium and high dose of ECC-BYP Ⅲ groups were decreased（P<0.05 or P<0.01），and the ET-1/PGI2 ratio of the rats in high of ECC-BYP Ⅲ group was decreased（P<0.05）.Compared with low dose of ECC-BYP Ⅲ group， the WT % and ET-1 in lung tissue were decreased（P<0.05 or P<0.01） and LA % was increased（P<0.01），the levels of TNF-α in lung tissue of the rats in medium dose of ECC-BYP Ⅲ group was decreased and the level of IL-6 and ET-1/PGI2 ratio in lung tissue of the rats in high dose of ECC-BYP Ⅲ group were decreased（P<0.05 ）. Conclusion ECC-BYP Ⅲ can reduce PH and wall thickness of the pulmonary arterioles， improve the lumen stenosis and pulmonary arteriolation，improve the pulmonary vascular remodeling，and its mechanism may be related to reducing the inflammation response of the pulmonary perivascular and improve unbalance of peripheral vasoconstriction vasular factor level/diastolic vascular factor level.

Key words: Effective-compound compatibility Ⅲ of Bufei Yishen prescription, Rats，SD, Pulmonary vascular remodeling, Inflammation response, Pulmonary arteriolation