益心方对模拟高原低氧环境大鼠相关指标及心肌损伤的干预作用

Intervention effect of Yixin formula on related indexes and myocardial injury of rats in simulated plateau hypoxia environment

目的探讨自拟中药合剂益心方对模拟高原低氧环境下SD大鼠心组织损伤的保护作用及其可能机制。方法 64只SD大鼠随机分为空白对照组、红景天组、丹参组、黄芪组、红景天丹参组、红景天黄芪组、丹参黄芪组及自拟益心方组,每组8只。给药组相对应的中药溶液灌胃,模型对照组灌胃等体积生理盐水,连续给药30天后,将大鼠放置于复合环境模拟实验低压氧舱内,模拟海拔5000米高度,48小时出舱后处死动物,采取血清及心脏组织,化学法测定超氧化物歧化酶(Super oxide dismutase,SOD)、丙二醛(Malondialdehyde,MDA)含量;ELISA 法测定心脏组织低氧诱导因子-1α(Hypoxia inducible factor-1,HIF-1α)、血管内皮细胞生长因子(Vascular endothelial growth factor,VEGF)、促红细胞生成素(Erythropoietin,EPO)含量及心肌酶五项:肌酸激酶( Creatine kinase,CK)、肌酸激酶同工酶( Creatine kinase isoenzyme MB,CK-MB)、乳酸脱氢酶( Lactate dehydrogenase,LDH)、天门冬氨酸氨基转移酶( Aspartate aminortransferase,AST)、羟丁酸脱氢酶(Hydroxybutyrate dehydrogenase,HBDH)水平。结果 VEGF、EPO、HIF-1α指标在各组间存在差异,差异有统计学意义(P<0.05)。VEGF、EPO、HIF-1α指标结果均提示空白组、益心方组与其余各组之间存在差异,差异有统计学意义(P<0.05)。SOD、MDA指标在各组间存在差异,差异有统计学意义(P<0.05),两指标的空白组、益心方组均与其余各组之间存在差异,差异有统计学意义(P<0.05)。益心方组血清心肌酶谱CK、CK-MB、LDH、AST、HBDH水平明显低于空白组及单味用药组,并且益心方组优于两两组合用药组并存在差异,差异有统计学意义(P<0.05)。结论自拟益心方对模拟低氧环境下损伤大鼠心肌组织具有一定的保护作用,其可能是通过提高SOD含量、降低MDA的生成,其机制可能与增加HIF-1α、VEGF、EPO表达、促进中小血管新生从而保护心肌细胞膜和细胞器的结构和功能,减轻因心肌细胞损伤而引起的CK、CK-MB、HBDH、LDH、AST的释放减少。

Objective To investigate the protective effect and its possible mechanism of Yixin formula,a self-made traditional Chinese medicine mixture,on myocardial injury in SD rats under simulated plateau hypoxia environment. Methods A total of 64 SD rats were randomly divided into the blank control group,the Herba Rhodiolae group,the Radix Salviae Miltiorrhizae group,the Radix Astragali seu Hedysari group,the Herba Rhodiolae and Radix Salviae Miltiorrhizae group ,the Radix Salviae Miltiorrhizae and Radix Astragali seu Hedysari group,and the self-made Yixin formula group,with 8 rats in each group. The corresponding Chinese medicine solution in the drug-administered group was intragastrically administered,and the model control group was intragastrically administered with the same volume of normal saline. After 30 days of continuous administration,the rats were placed in a hypoxic oxygen chamber of a simulated environment simulation experiment,simulating an altitude of 5000 m,48 hours. The animals are killed after being taking out of the cabin,and were taken serum and heart tissue,after 48 hours. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by chemical method. The levels of hypoxia inducible factor-1 (HIF-1α),vascular endothelial growth factor (VEGF),erythropoietin (EPO) and five items of myocardial enzymes: creatine kinase (CK),creatine kinase isoenzyme MB, CK-MB ),lactate dehydrogenase (LDH),Aspartate aminotransferase (AST),hydroxybutyrate dehydrogenase (HBDH) were measured by ELISA method. Results The indexes of VEGF,EPO and HIF-1α were different among the groups,and the differences was statistically significant ( P <0.05). All the results of VEGF,EPO and HIF-1α indicated that there were differences among the blank group, Yixin formula group and the other groups ( P <0.05). The differences are statistically significant( P <0.05). The indexes SOD and MDA were different among the groups,and the differences were statistically significant ( P <0.05 ). There were index differences among the blank group and Yixin formula group and the other groups and the differences were statistically significant ( P <0.05). Besides,the levels of serum myocardial enzymes CK,CK-MB,LDH,AST and HBDH in Yixin formula group were significantly lower than those in the blank group and the single drug group. Moreover, Yixin formula group was superior to the drug combination groups and the differences were statistical significance ( P <0.05). Conclusion Apparently,the self-made Yixin formula has a certain protective effect on myocardial tissue of rats injured under simulated hypoxic environment. And this kind of protective effects may be achieved by the methods of increasing SOD level and decreasing MDA production. The mechanism may be related to the a series of factors,such as increasing HIF-1α,VEGF,EPO expression,promoting angiogenesis in small and medium vessels so as to protect the structure and function of myocardial cell membrane and organelles,and reducing the release of CK,CK-MB,HBDH,LDH,AST caused by myocardial cell injury.