| Objective:Induced the model of nonalcoholic fatty liver disease （NAFLD） withhigh fat diet, and intervened with telmisartan. Tested the resistin level inserum and the expression of resistin in omental and liver tissue. Then,estimated the effect of telmisartan on NAFLD model with the expression ofresistin, and to further clarify the therapeutic mechanism of telmisartan innon-alcoholic fatty liver disease.Methods:1Animal model: Selected male SD （Sprague Dawley） rats, the normalcontrol（NC） group was fed with normal diet, NAFLD model group was fedwith high fat diet （84%cholesterol+5%ordinary feed+1%egg yolkpowder+10%lard）. During the experiment, the animal was free to eat and todrink.2Designs experiment:35SD rats were randomly divided into normalcontrol group （NC, group, n=10） with normal diet, high fat diet group （FC,group, n=15） and high fat+telmisartan intervention group （FT, group,n=10）with high fat diet; At the end of12th week, chose the five rats fromeach group in NC group and FC group randomly to put them with liver tissueHE staining, then, to make sure if modeling success. After that, FT group weregiven telmisartan (5mg.kg-1.d-1) by intragastric administration and continuehigh-fat diet. NC group and FC group were given the same Sodium Chlorideby intragastric administration intervention, once daily for four weeks.3Changes of body weight in rats: Weighted the body weight withelectronic balance every week and recorded changes of body weight.4Liver histological examination: Liver histology: the application ofparaffin section, with hematoxylin and eosin （HE） staining method, observethe change of liver pathology by light microscopy. 5Detected resistin in liver tissue, omentum and blood serum: Theexpression of resistin in liver tissue and greater omentum was detected byimmunohistochemical method, the level of resistin in blood serum wasmeasured by radioimmunoassay.6Detection of serum biochemistry: Using automatic biochemicalanalyzer to detected the changes of aminotransferase, blood lipids and otherbiochemical markers in blood serum.7Determined the level of fasting serum insulin （FINS） byradioimmunoassay, according to the HOMA model to calculate the index ofinsulin resistance in IRI=（FINSxFBG）/22.5.8Using the software of HMIAS-2000microscopic color image analysissystem in20times the objective lens to calculate average surface density asthe relative expression amount of resistin in semi quantitative analysis.Results:1Changes of body weight of rats in each group: Fed with high fat dietfor12weeks, the rats of the FC group （368.78±27.65） and the FT group（363.38±26.49） have no difference in body weight （P=0.899>0.05）, the bodyweight of these groups were significant higher than the NC group（335.67±19.50）（P<0.05）; After4weeks drug intervention, the FT group（334.50±33.18） weight has decreased than the FC group （399.44±24.91）（P<0.01）; the FT group （334.50±33.18） weight was higher than NC group（332.67±13.01） slightly, but they did not have statistical difference（P=0.876>0.05）.2General and histopathological changes: the liver of the NC group ratswas reddish-brown appearance, smooth and shiny; the liver cells of the NCgroup in HE staining without fatty degeneration and inflammatory infiltration.The liver of the FC group rats had the appearance of yellow, rough, dull andgreasy feeling; the liver cells of the FC group in HE staining had the bullousfat droplets storage, ballooning degeneration, cell necrosis and the mixedinflammatory cells infiltration in lobules of liver and liver portal canal; Afterdrug intervention, the rats of the FT group had an improve in fatty degeneration of liver cells and the inflammation grade classification with theFC group significantly.3Changes of serum biochemical indexes:（1） The level of alanine aminotransferase （ALT） and aspartateaminotransferase （AST） in serum: the ALT of the FC group（32.68±12.26）wasstriking higher than the NC group（15.21±1.01）（P<0.01）, while the ALT ofthe FT group（16.71±1.11）had a sharp decline than the FC group（P<0.01）,but the FT group did not have a difference with the the NCgroup（P=0.78>0.05）；the AST of the FC group（33.31±5.78）was higher thanthe NC group（21.64±1.20）（P<0.01）, the AST of the FT group（20.76±2.20）had an obvious decrease than the FC group（P<0.01）, but the FT group did nothave a difference with the the NC group（P=0.742>0.05）.（2） The level of TC and TG in blood serum: Compared with the NCgroup（TC1.21±0.17, TG0.46±0.07）, the FC group（TC2.05±0.18, TG0.82±0.07） and the FT group（TC1.59±0.13, TG0.55±0.14） were rose sharply（P<0.01）; however, the FC group was still higher than the FT group.（3） FBG, INS and HOME-IR value: Compared with the NC group（5.79±0.23）, the FBG of the FC group （11.83±0.70） was significantlyincreased （P<0.01）; the FT group （9.78±0.78） was lower than the FC group（P<0.01）. Compared with the NC group （18.27±1.44）, the INS of the FCgroup （27.97±2.36） was significantly increased （P<0.01）; the FT group（22.17±1.21） was lower than the FC group （P<0.01）, but it was still higherthan NC group. The HOME-IR value of the NC group （4.71±0.44） wasdecreased significantly, compared with the FC group （14.70±1.37）（P<0.01）;Compared with the FC group, the FT group （9.62±0.70） was decreasedsignificantly （P<0.01）.4Changes of the level of resistin in liver, omentum tissue and bloodserum:（1） Changes of resistin in liver tissue: Compared with the NC group（0.13±0.02）, the FC group （0.34±0.04） was significantly increased （P<0.01）,the FT group （0.21±0.02） was decreased compared with the FC group （P<0.01）, but it was still higher than the NC group （P<0.01）.（2） Changes of resistin in omental tissue: Compared with the NC group（0.12±0.01）, the FC group （0.28±0.04） was significantly increased （P<0.01）,the FT group （0.17±0.01） was decreased compared with the FC group（P<0.01）, but it was still higher than the NC group （P<0.01）.（3） Changes of resistin in serum: the FC group （27.78±2.00） wassignificantly higher than the NC group （15.46±1.00）（P<0.01）, the FT group（21.14±3.02） was lower than the FC group （P<0.01）, but it was still higherthan the NC group （P<0.01）.Conclusion:The model of NAFLD has been induced successfully by high fat dietafter16weeks. The expression of resistin in omental was increased in NAFLD,resulting resistin in liver tissue and serum was significantly increased, leadingto insulin resistance; Telmisartan could improve lipid metabolism disorder andinsulin resistance, weight control, improve the development of NAFLD onliver damage, decrease the expression of resistin in omental and liver tissue,thereby reducing the serum resistin level, improving hepatic steatosis andinflammation. |
PDF Full Text Request