| Objective: The model of non-alcoholic fatty liver disease (NAFLD)was established by high-fat diet, and intervened with telmisartan. The leptinlevels in omentum tissue and serum, as well as the expressions of leptinreceptor in liver tissue were detected and analysed. The study of influence oftelmisartan on the secretion of leptin and expression of leptin receptor inNAFLD of rats would provide us new understanding and knowleges about themechanisms of therapeutic efficacies of telmisartan on NAFLD.Methods:1Animal model:Selected male Sprague Dawley rats and normal control group were fedwith common diet; model group were fed with high-fat diet, the formula is:84%normal diet,1%cholesterol,5%egg yolk powder, and10%lard. Duringthe experiment, rats were free to eat and drink.2Designs experiment:35male SD rats were randomly divided into:1. NC group (n=10) normalchow-fed controls;2.FC group (n=15) high fat-fed control group;3.FT group(n=10) high fat-fed with telmisartan group; At the end of12th week,5ratswhich were randomly selected from NC group and the5rats of FC group wereput to do liver tissue HE staining and to determine if model success. Then FTgroup was given telmisartan (5mg.kg-1.d-1) by intragastric administration andcontinued high-fat diet. NC group and FC group were given the same SodiumChloride by intragastric administration intervention, once daily for four weeks.3The changes of body weight:Body weight were weighted from electronic balance.4Liver histological examination:The paraffin sections, HE staining, light microscopy of liver pathology. 5the method of detect the leptin in omentum adipose tissues and serum, aswell the leptin receptor in liver tissue:the leptin in omentum adipose tissues and the leptin receptor in livertissue were used Immunohistochemical method. Serum leptin was byRadioimmunoassay.6Blood serum biochemistry inspection:Detection changes of serum lipids and aminotransferase, and otherbiochemical markers were using automatic biochemical analyzer.7Fasting serum insulin (FINS) level was measured by radioimmunoassay.Calculated insulin resistance index (IRI) according to HOMA model,IRI=(FINSx FBG)/22.5.8Using multifunctional pathological image analysis to measure the omentumleptin, hepatic steatosis, liver leptin receptor expression area percentage, selecteach slice around the central five regions,20times of the objective lens with acalculated average area density (the positive area and Statistics field areapercentage), results averaged.Results:1Changes in body weight of rats in each group：The rats weight were about200g when just purchased, randomized.Compared the weight before the experiment was no difference betweendifferent groups (219.00±2.00,203.78±8.12,204.38±8.23)(P>0.01), Thesegroups body weight baseline is consistent with good comparability.High-fat group and the treatment group by the high-fat diet for12weeks,The body weight of rats stabilized,and the body weight of the two groups ofrats were no difference(368.78±27.65,332.67±13.01)(P<0.01). The weight ofthe high-fat diet rats were higher than the normal control group (368.78±27.65,335.67±19.50)(P<0.05). After four weeks drug intervention, the treatmentgroup(334.50±33.18) body weight was significant decreased than fat group(399.44±24.91), but the weight of the treatment group is still higher than thenormal group(332.67±13.01), the difference was significant (P<0.01).2General changes in the liver and histopathological changes： Histological analysis: Steatosis and inflammation were not seen innormal controlled group, while severe lipid degeneration was found in modelgroup(P<0.01), especially around central vein. Lobular inflammation,periportal inflammation and degeneration, focal necrosis were found in themodel group. These have a significant difference between normal group andmodel group (P<0.01). Steatosis showed be improved in the treatment group,compared with model group(P<0.01).Inflammation showed be significantimproved in the treatment group, compared with model group(P<0.01).3Serum biochemical index：(1) Serum ALT and AST level(U/L) of model group(32.68±12.26and33.31±5.78, respectively) were increased significantly compared with normalgroup(15.21±1.01and21.64±1.20)(P<0.01). Compared with model group,ALT and AST level of the treatment group(16.71±1.11and20.76±2.20,respectively)were decreased markedly (P<0.01).(2) Serum TC and TG level (mmol/L) of model group(2.02±0.18,0.82±0.07,respectively) were increased significantly compared with normal group(1.21±0.17,0.46±0.07, respectively)(P<0.01,0.01, respectively).The value ofthe treatment group drop to (1.59±0.13,0.55±0.14, respectively), comparedwith that of model group have no statistical difference(P>0.05).(3)Serum glucose and HOMA-IR:Fasting blood glucose(mmol/L)level of model group(11.83±0.70) wasincreased markedly compared with normal group(5.79±0.23)(P<0.01),Compared with model group, the treatment group(9.78±0.78) wassignificantly decreased. Two groups have statistical difference(P<0.01). modelgroup of HOMA-IR(14.70±1.37) was increased markedly compared withnormal group(4.71±0.44)(P<0.01), Compared with model group, the treatmentgroup(9.61±0.70)was significantly decreased, these groups have statisticaldifference(P<0.01).4The changes of leptin in Omentum, serum, liver and leptin receptor in liver:(1)Omentum leptin changes：compared with normal group (0.12±0.01), the model group (0.29±0.04) was increased significantly(P<0.01). Compared with model group, thetreatment group(0.16±0.01)was decreased significantly, these have statisticaldifference(P<0.01).(2) Serum leptin changes:Compared with normal group(1.41±0.06), the model group (1.70±0.08)was increased significantly (P<0.01)， compared with model group, thetreatment group (1.48±0.06)was decreased significantly, these groups havestatistical difference(P<0.01).(3) Changes in the distribution of the hepatic leptin:Compared with normal group(0.07±0.02), the model group (0.25±0.04)was increased significantly(P<0.01). Compared with model group, thetreatment group(0.15±0.01)was significantly decreased, two groups havestatistical difference(P<0.01).(5) Changes in liver leptin receptor:Compared with normal group (0.34±0.09), the model group (0.13±0.01)was decreased significantly (P<0.01), Compared with model group, thetreatment group(0.24±0.02)was incresed significantly, these groups havestatistical difference(P<0.01).Conclusion:Twelve weeks of high-fat diet induced non-alcoholic fattyliver disease of rats successfully. Omentum leptin secretion was induced bymode of endocrine and serum leptin levels increased significantly, while liverleptin receptor expression was decreased in rats of NASH. These indicated thepresence of leptin resistance. Telmisartan could improve lipid disorders, liverfunction and insulin resistance by controling weight gain, reducing omentumleptin secretion and serum leptin levels, increasing leptin receptor expressionin liver and, therefore, reducing leptin resistance. |
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