Effects Of Long-term Endurance Swimming Training On Hepatocytes Apoptosis Of High-fat-diet Rats

PURPOSE: NASH including simple fat accumulation to nonalcoholic steatohepatitis and hepatocirrhosis. NASH is an acknowledged pathogeny of hepatocirrhosis and hepatofibrosis, and its primary dangerous factors are obesity, type 2 diabetes and high blood-fat. NASH is the common cause for hypohepatia, the incidence of this disease is highly higher than the infect incidence of third liver virus. It has been testified that there is a tight relationship between apoptosis and the occurrence of nonalcoholic steatohepatitis induced by obesity, diabetes and hyperlipidemia. Besides different degree of pathological changes in histology, there is a remarkable increase in hepatocytes apoptosis.In this paper we built a rat model of NASH, and we bring 8-12 weeks swimming exercise pressure to bear on rats. Through studying the influence of 8-12 weeks endurance exercise on hepatocytes apoptosis of high-fat diet rats, we discuss the mechanism of hepatocytes apoptosis in the process of NASH and provide academic proof for the precautionary and sanative effect of long-range endurance on NASH.METHODS: Forty-four 1-month-old male Sprague Dawley rats were randomly divided into six groups: 8 week control group(C8, n=6), 8 week high-fat diet group(H8, n=8), 8 week high-fat diet concomitant with exercise-trained group (HE8, n=8), 12 week control group(C12, n=6), 12 week high-fat diet group(H12, n=8), 12 week high-fat diet concomitant with exercise-trained group (HE12, n=8). The rats in H and HE groups were fed on high fat diet, and the rats in C groups were fed with standard rodent chow and libitum. Lipid percentage in high fat diet and standard diet is 35% and 11%, respectively. Animals in HE8 group were trained by swimming exercise for 8 weeks (90min/day, 5days/week) and the rats in HE12 group were trained for 12 weeks. The rats in groups of C8, H8 and HE8 were killed after 8 weeks, The rats in groups of C12, H12 and HE12 were killed after 12 weeks. By using flow cytometery method, the authors detected the apoptosis of rat hepatocytes, the content of FFA in liver, the concentrations of super superoxide dismutase(SOD), amount of malonaldehyde (MDA), the concentration of Ca²⁺ in hepatocytes, mitochondrial membrane potential and Bcl-2 protein expression in hepatocytes.RESULTS: The results reveal that after exercise, the rat hepatocytes apoptosis was decreased significantly (H: 30.75±5.99% vs HE:20.47±7.19%, P<0.05), and the precautionary and sanative effect on NASH was remarkable in 12 week groups than 8 week groups.There is a series of changes in 12 weeks endurance group, such as following: Relation to the data of H12 group, the body weight (H:490.63±40.75g vs HE:437.5±19.82g, P<0.01)and the liver weight(H:16.21±2.23g vs HE:14.03±1.89g,P<0.05)of rats were decreased significantly. The content of FFA in liver was decreased significantly (H:305.48±69.24 ^mol/mg prot vs HE:209.65±57.36 ,umol/mg prot, P<0.05), the concentrations of liver SOD(H: 205.13+43.74 NU/mg prot vs HE: 257.43+48.73 NU/mg prot,P<0.05)was increased while that of MDA decreased significantly (H:5.31±1.46 nmol/mg prot vs HE:2.84±0.92 nmol/mg prot, P<0.01), the ratio of SOD and MDA was increased significantly(H:39.76±7.58 vs HE:97.45±30.28, P<0.01).The mitochondrial membrane potential was increased significantly (H:0.75±0.20 vs HE:1.22±0.11, P<0.05), Bcl-2 protein expression was increased significantly (H:0.86±0.07 vs HE:0.96±0.07, P<0.05).CONCLUSIONS: 1) Long-range endurance exercise have a regulative effect on the livability of hepatocytes and may ultimately inhibit the liver injure and improves liver function by restrain the elevated apoptosis and the malignant proliferation of hepatocytes, which can provide academic proof for the precautionary and sanative effect of long-range endurance on NASH.2) Long-range endurance exercise can restrain the hepatocytes apoptosis by result in the elevation of antioxidant system capability possibly through decreased the lipid peroxidation and accelerate the elimination of lipid peroxidation products, and cause the enhance of relative adaptability and elevation of mitochondrial membrane potential.3) Long-range endurance exercise can result in the significant decrease of hepatocytes apoptosis possibly through up-regulate the Bcl-2 protein expression.