Plateau Exposure Time And Salvia Miltiorrhiza Combined Six Invigorating Drugs Effects On Hypoxic Pulmonary Hypertension

Objective:In plateau hypoxia environment,to explore the different altitude and plateau exposure time of hypoxic pulmonary hypertension and the effect of altitude and time determine approximate pathological changes,thus preventive study,therefore,to further explore gansu west sage six air compensating medicine of hypoxic pulmonary hypertension prevention effect and possible mechanism of prevention and screening effect is a good medicine for,in order to provide a theoretical basis for the search of HPH treatment drugs from Traditional Chinese medicine.Methods:1.To explore the effect of exposure time on HPH in the plateau,24 male SD rats were randomly divided into 4 groups,6 rats in each group: control group(30 d),control group(60 d),high altitude group(30 d)and high altitude group(60 d).m PAP and RVHI were measured at 30 d and 60 d,respectively,and histopathological changes were observed by HE staining.The levels of HIF-2α,EGLN1,e NOS,Apo A5,VEGF,BNP and TGF-β in cardiopulmonary tissues of rats in 4 groups were detected by real-time fluorescence quantitative assay(q RT-PCR).2.To investigate the effect of Salvia przewalskii combined with seven qi-invigorating and blood-promoting drugs on HPH,60 SD rats were randomly divided into 10 groups,each group of 6,the control group,model group,positive control group,Salvia przewalskii group,Salvia przewalskii-astragalus membranaceus group,Salvia przewalskii-dangshen,Salvia przewalskii-hand reference group,Salvia przewalskii-rhodiola,Salvia przewalskii-atractylodes,Salvia przewalskii-acanthopanax group.Each drug administration group was given corresponding drug intervention.After 30 days of intervention,m PAP,RVHI and HE staining were measured to observe the cardiopulmonary histopathological changes.(4)The m RNA expression levels of HIF-1α,BMP4,TRPC1,TRPC6 and ORAI1 in rat lung tissue were determined by QRT-PCR to explore the mechanism of drug prevention.Results:1.The results of exploring the effect of exposure time on HPH in plateau showed that:(1)After 30 days of exposure,m PAP and RVHI in altitude group were higher than those in control group(P < 0.05).After 60 days of exposure,m PAP in the high-altitude group was reduced to 30 mm Hg,with no statistical difference compared with the control group.m PAP and RVHI of rats in high altitude group 60 days were lower than those in high altitude group 30 days(P < 0.05).(2)Histopathological results showed that,compared with the control group,the pulmonary artery wall of rats in the two groups of high altitude group was significantly thickened.Severe bleeding in liver tissue;The glomerular basement membrane was thickened and bleeding was severe.Myocardial space was enlarged and the whole arrangement was disordered.At the altitude of 4260 m,with the increase of exposure time,the damage degree of each organ tissue was aggravated.(3)The m RNA expressions of e NOS,EGLN1,HIF-2α,VEGF and TGF-1β in lung tissues of rats at 60 d altitude were higher than those at 30 d altitude(P < 0.05).(4)The m RNA expressions of e NOS,EGLN1,HIF-2α,BNP and Apo A5 in heart tissue of rats at 60 d altitude were higher than those at 30 d altitude(P < 0.05).2.The results of exploring the effects of Salvia ganesi combined with seven qi replenishing drugs on HPH showed that:(1)Compared with the control group,the mean pulmonary artery pressure in the high altitude group was significantly increased(P < 0.05);Compared with the high altitude group,each dose group rats mean pulmonary artery pressure decreased significantly(P < 0.05),with acetazolamide positive control group,Salvia przewalskii,Salvia przewalskii-dangshen,Salvia przewalskii-rhodiola group is most obvious reduction,numerical and altitude group had no statistical difference(P >0.05);(2)Compared with the control group,the lung tissue injury in the model group was serious,and the arterial wall thickening was more obvious.Compared with the high altitude group,the lung tissue injury in the drug administration groups was lighter,and the lung tissue injury in the Salvia przewalskii-Codonopsis pilosula group and Salvia przewalskii-rhodiola rosea was the least.(3)Compared with the control group,the expression of HIF-1α,BMP4,TRPC1,TRPC6,ORAI1 in the high-altitude group was increased,and the difference was significant(P < 0.05);compared with the high-altitude model group,the expression of HIF-1α,BMP4,TCRP1,TCRP6,STIM1 and ORAI1 were decreased,and the difference was significant(P < 0.05).Conclusion:(1)Altitude and altitude exposure time had influence on HPH disease,that is,m PAP was the highest at altitude of 4260 m for 30 d,but with the extension of exposure time,altitude adaptive gene expression increased,pulmonary vascular dilation,compensatory reduction of m PAP,but pathological damage of heart,liver,spleen and lung tissues increased.(2)Salvia przewalskii combined with seven drugs for supplementing qi and promoting blood circulation can reduce m PAP and RVHI in rats,have protective effect on rat heart and lung tissue,and have preventive effect on HPH disease.Salvia przewalskii-Codonopsis and Salvia przewalskii-rhodiola have better effects.It is possible to prevent HPH by regulating the m RNA expression of HIF-1α,BMP4,TRPC and SOCC.