| Objective:To investigate the protecting effects and mechanism of total glycosides of paeonyon liver damage of NAFLD rats fed with high-fat and fructoseMethods:Nonalcoholic fatty liver disease rats model was induced by high-fat diet and10%fructose. SD rats（male and female in equal） were randomly divided into normal groupand model group. The normal rats were raised by standard animal diet and clean tapwater, while the model rats were fed with high-fat diet and10%fructose for6weeks,then randomly took out2rats from each group and caught out liver for HE staining toobserve hepatocyte pathological changes. Hepatic cells of normal group were regular,hepatic cord rowed neatly, hepatic sinusoid clearly, and no obvious pathologicalchanges. While hepatic cells of model group were obviously swollen and circular, aswell as a large number of hepatic cells had granules and emerged vacuolesdegeneration, cytoplasm was filled with any size lipid droplets, hepatic cord roweddisorder, hepatic sinusoid unclearly. It turned out that successfully copyingnonalcoholic fatty liver disease rats model. According to the weight, model groupwere randomly divided into4groups: nonalcoholic fatty liver group, metformin group(200mg·kg-1), low-dose total glucosides of paeony group(100mg·kg-1) and high-dosetotal glucosides of paeony group(200mg·kg-1). All rats were treated for4weeks. Allof normal group and nonalcoholic fatty liver group rats were gavaged with distilledwater (10ml﹒kg-1), and therapeutic groups were gavaged with relevant drug. During4-week treatment, general state, body weight were observed. To execute all of rats in24h at the end of treatment, HE staining to observe hepatocyte pathological changes.Blood was collected to detect content of fasting blood glucose, insulin, totalcholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoproteincholesterol, liver function index, collagen Ⅲ,collagen Ⅳ, malondialdehyde,apelin-36and visfatin, and the activity of superoxide dismutase, glutathion peroxidase. Count liver index, detecting the activity of superoxide dismutase，content ofmalondialdehyde and liver lipid of liver tissue. Protein expression of p-ERK1/2,TLR4and TLR9in liver tissue were detected by Western-Blot assay.Result:（1） Hepatic cells of model group were obviously swollen and circular, as well asa large number of hepatic cells had granules and emerged vacuoles degeneration,cytoplasm was filled with any size lipid droplets, hepatic cord rowed disorder, hepaticsinusoid unclearly. After treated by total glucosides of paeony and metformin, hepaticpathological damage were significantly inhibited.（2） Compared with normal group, content of liver lipid were increased and iverfunction index were disorder obviously in model group （P<0.01）. Content of fastingblood glucose, insulin, total cholesterol, triglyceride, low-density lipoproteincholesterol, collagen Ⅲ, collagen Ⅳ, apelin-36and vifatin were increased clearly,while content of high-density lipoprotein cholesterol were decreased（P<0.01）.Activity of superoxide dismutase and glutathion peroxidase were decreased, andcontent of malondialdehyde was increased obviously （P<0.01）. Protein expression ofp-ERK1/2,TLR4and TLR9in liver tissue were increased obviously （P<0.01）.（3） Compared with model group, both content of liver lipid and iver functionindex were decreased significantly in high-dose total glucosides of paeony group,low-dose total glucosides of paeony group and metformin group （P<0.01,P<0.05）.（4） Compared with model group, content of fasting blood glucose, insulin, totalcholesterol, triglyceride and low-density lipoprotein cholesterol were decreased andcontent of high-density lipoprotein cholesterol were increased significantly inhigh-dose total glucosides of paeony group, low-dose total glucosides of paeonygroup and metformin group,（P<0.01,P<0.05）.（5） Compared with model group, activity of superoxide dismutase and glutathionperoxidase were increased, and content of malondialdehyde was decreased inhigh-dose total glucosides of paeony group, low-dose total glucosides of paeonygroup and metformin group（P<0.01,P<0.05）. （6） Compared with model group, content of collagen Ⅲ, collagen Ⅳ, apelin-36and vifatin were decreased obviously in high-dose total glucosides of paeony group,low-dose total glucosides of paeony group and metformin group （P<0.01,P<0.05）.（7） Compared with model group, protein expression of p-ERK1/2,TLR4andTLR9in liver tissue were decreased obviously in high-dose total glucosides of paeonygroup, low-dose total glucosides of paeony group and metformin group （P<0.01）.Conclusion:（1） Total glucosides of paeony exerted protective effects on liver damage innonalcoholic fatty liver rats.（2） The possible mechanisms of protective effects of total glucosides of paeonyon liver damage in nonalcoholic fatty liver rats may be related to interposeERK-TLRs channel, which consequently resulted in content of apelin and visfatinwere decreased, insulin resistance were improved, antioxidant ability were enhancedand inflammation were relieved. |
PDF Full Text Request