Effect Of Salidroside On The Myocardial Mitochondrial Biogenesis Regulatory Factors Of Rats After Acute Exhaustive Exercise At Different Time

Objective：Peroxisome proliferator-activated receptor γ，coactivator1α(PGC-1α), Nuclear respiratory factors NRF-1and NRF-2are the key factorsof the regulation of mitochondrial biogenesis，moderate exercise can induce itsexpression, thereby stimulating mitochondrial biogenesis. Through theestablishment of a single bout of exhausted swimming model, our work is toresearch the protein and gene expression of mitochondrial biogenesis relatedfactors, PGC-1α, NRF-1and NRF-2, at different time after exhaustive exercise.In order to investigate the effects of exhaustive exercise on mitochondrialbiogenesis, and the effect of Salidroside (SAL) of rats after acute exhaustive.Methods：1A total of104health male Sprague Dawley rats (average weight (120±20g)) were randomly divided into13groups(n=8in each group)，includingsedentary control group, exhausted exercise groups (0，6，12and24hours afterexhausted exercise), low-dose SAL and exhausted exercise groups (0，6，12and24hours after exhausted exercise), high-dose SAL and exhausted exercisegroups (0，6，12and24hours after exhausted exercise). Sedentary controlgroup and exhausted exercise groups were administered with saline（10ml/kg）intragastrically for14days. Low-dose SAL and exhausted exercise groups andhigh-dose SAL and exhausted exercise groups were administered withlow-dose SAL (100mg/kg) or high-dose SAL (300mg/kg) intragastrically for14days. Then exhausted exercise model was established. Exhaustive exercisemodel is a single bout of exhausted swimming model, according to Thomasstandards. Finally there were6rats in each group enters the statistical dataanalysis of experimental, excluding who died in the single bout of exhaustedswimming process of choking or unexplained deaths during the experiment. 2By ELISA kit to detect lactate dehydrogenase (LDH), creatine kinaseisoenzyme (CK-MB), troponin (cTnI) in serum, to verify the extent ofmyocardial damage by Exhaustive exercise.3Using fluorescence quantitative polymerase chain reaction (PCR) todetect the gene expression of PGC-1α, NRF1and NRF2each group ratsmyocardial.4Western blot was used to detect the protein expression of PGC-1α,NRF-1and NRF-2.Results:1Compared with control group (0.92±0.04), level of LDH (U/L) in theblood serum of each group after exhausted exercise, low-dose SAL and6h(1.14±0.10),12h (1.10±0.07) after exhausted exercise, high-dose SAL and12h (1.09±0.12) after exhausted exercise were Significantly higher(P＜0.05).The content of LDH in12h was the highest after exhausted. With the sametime of exhaustive group, low-dose SAL of0h after exhausted exercise,high-dose of0h and6h after exhausted exercise, the levels of LDH decreasedsignificantly (P＜0.05).2Compared with control group (2.11±0.18), level of CK-MB (ng/ml) inthe blood serum of other groups were Significantly higher(P＜0.05). The levelof CK-MB in6h was the highest after exhausted. With the same time ofexhaustive group, low-dose SAL of6h after exhausted exercise, high-dose of0h and6h after exhausted exercise, the levels of LDH decreased significantly(P＜0.05).3Compared with control group (144.61±12.71), level of cTnI (pg/ml) inthe blood serum of each group after exhausted exercise, low-dose SAL and6h(186.77±9.54),12h (180.29±7.42) and24h (168.69±16.43) after exhaustedexercise, high-dose SAL and6h (178.93±17.58),12h (1.09±0.12) afterexhausted exercise were Significantly higher(P＜0.05). The level of cTnI in12h was the highest after exhausted. With the same time of exhaustive group,high-dose of12h after exhausted exercise, the levels of cTnI decreasedsignificantly (P＜0.05). 4The gene expression of PGC-1α of other groups were significantlyhigher than that of control group(P＜0.05), and the longer the time expressiondecreased, medication group was significantly higher than that of exhaustivegroup(P＜0.05). With the same time of exhaustive group, each group oflow-dose and high-dose groups, the levels of PGC-1α mRNA increasedsignificantly (P＜0.05). Low-dose groups and high-dose groups hadsignificant difference (P＜0.05).5The gene expression of NRF-1of other groups were significantlyhigher than that of control group(P＜0.05), and6h groups was the highest.With the same time of exhaustive group, low-dose and0h and6h afterexhaustive exercise, each high-dose group, the levels of NRF-1mRNAincreased significantly (P＜0.05). Low-dose groups and high-dose groups hadsignificant difference (P＜0.05).6In addition to exhaustive24h group after exhausted exercise, the geneexpression of NRF-2of other groups were significantly higher than that ofcontrol group(P＜0.05), and6h groups was the highest. With the same time ofexhaustive group, except low-dose and12h after exhaustive exercise, thelevels of NRF-2mRNA increased significantly (P＜0.05). Low-dose groupsand high-dose groups had significant difference (P＜0.05).7Compared with control group (0.9419±0.0226), level of the proteinexpression of PGC-1α in rats myocardial of the low-dose SAL and6h (1.0932±0.0772) and high-dose SAL and6h (1.2348±0.0740) after exhaustedexercise were Significantly higher(P＜0.05).0h (0.3564±0.0550)，6h (0.7990±0.0312)，12h (0.6086±0.0256) and24h (0.5309±0.0302) after exhaustedexercise, low-dose SAL and0h (0.5514±0.0319),12h (0.8410±0.0295),24h(0.7405±0.0303) after exhausted exercise, high-dose SAL and0h (0.4831±0.0449),24h (0.6603±0.0231) after exhausted exercise were Significantlylower(P＜0.05). With the same time of exhaustive group, each group oflow-dose and high-dose groups, the levels of PGC-1α protenin increasedsignificantly (P＜0.05). Low-dose groups and high-dose groups hadsignificant difference (P＜0.05). 8Compared with control group (0.8574±0.0180), level of the proteinexpression of NRF-1in rats myocardial of the low-dose SAL and6h (0.9352±0.0190),24h (0.9252±0.0344) after exhausted exercise were Significantlyhigher(P＜0.05).0h (0.7313±0.0343)，6h (0.7132±0.0377) and24h(0.5910±0.0404) after exhausted exercise, low-dose SAL and0h (0.7073±0.0241) after exhausted exercise, high-dose SAL and0h (0.6135±0.0384),12h (0.5646±0.0217),24h (0.5617±0.0283) after exhausted exercise wereSignificantly lower(P＜0.05). With the same time of exhaustive group,low-dose SAL and6h,12h and24h after exhausted exercise wereSignificantly higher(P＜0.05). Low-dose groups and high-dose groups hadsignificant difference (P＜0.05).9Compared with control group (0.7523±0.0333), level of the proteinexpression of NRF-2in rats myocardial of the low-dose SAL and12h (1.0281±0.0954) and high-dose SAL and6h (1.0295±0.0506),12h (1.1343±0.0632),24h (0.8346±0.0371) after exhausted exercise were Significantlyhigher(P＜0.05).0h (0.3624±0.0532)，6h (0.6601±0.0231),24h (0.6752±0.0337) after exhausted exercise, low-dose SAL and0h (0.5509±0.0374),24h(0.6725±0.0122) after exhausted exercise, high-dose SAL and0h (0.6020±0.0173) after exhausted exercise were Significantly lower(P＜0.05). Theexpression of NRF-2protein of each group in12h was the highest and in0hwas the lowest. With the same time of exhaustive group, low-dose and0h,6h,and12h, each group of high-dose groups, the levels of NRF-2proteninincreased significantly (P＜0.05). Low-dose groups and high-dose groups hadsignificant difference (P＜0.05).Conclusion:1Acute exhaustive exercise cause myocardial damge. Exhaustiveexercise first stimulates the expression of PGC-1α mRNA, the expression ofNRF-1and NRF-2mRNA then induced by PGC-1α. And mitochondrialbiogenesis is the performance of rats in the stress response stimulation.2Salidroside has protective effects of myocardial damge after exhaustive exercise. The molecular mechanism may be that Salidroside can promotemitochondrial biogenesis through stimulating the expression of PGC-1α,NRF-1, NRF-2mRNA and the expression of PGC-1α, NRF-2protein.