普罗布考干预大鼠非酒精性脂肪肝形成的作用及机制研究

目的：探究普罗布考对大鼠非酒精性脂肪肝形成作用的干预情况及干预机制。方法选取30只SD大鼠，将其随机分为空白组、高脂组及研究组，每组10只。给予相应喂养方法，通过高脂饮食诱发实验大鼠出现NAFLD，建立模型，喂养18周后，处死全部大鼠，并进行血脂及肝功能相关指数，即TC、TG、AST、ALT及HDL与LDL水平，计算肝脏指数同时检测其肝脏组织FXR、SHP及SREBP-1c mRNA表达情况。结果3组大鼠肝脏病变程度均以高脂组最高，空白组最低，研究组脂肪性病变、炎性程度及纤维化病变评分分别为（2?．97±0．18）分、（1．29±0．27）分及（0．05±0．02）分，均位于其他2组评分之间。高脂组与研究组TC、ALT、AST及LDL与空白组比较均明显升高，且高脂组升高程度更为明显（ P ＜0．05），空白组FXR、SHP及SREBP-1c的mRNA水平分别为（0．92±0．42）β-actin、（1．01±0．60）β-actin、（0．68±0．27）β-actin，各检测项目均显著高于高脂组（ P ＜0．05），研究组FXR、SHP的mRNA表达水平位于其他2组之间，分别为（0．28±0．13）β-actin及（0．42±0．23）β-actin，差异有统计学意义（ P ＜0．05），而SREBP-1c的mRNA表达水平为（0．68±0．22）β-actin，与空白组基本相同（ P ＞0．05）。结论普罗布考对由高脂饮食导致的大鼠NAFLD症状具有一定的预防作用，可明显减轻由该因素导致的大鼠肝脏出现脂肪性样变情况，其预防机制为该药物提高了大鼠机体的抗氧化能力，从而降低了组织出现氧化应激而导致的损伤。

Study on the effects and action mechanism of probucol on the pathogenesis of nonalcoholic fatty liver in rats

Objective To observe the effects of probucol on the pathogenesis of nonalcoholic fatty liver ( NAFLD) in rats,and to explore its action mechanism.Methods Thirty SD rats were randomly divided into blank control group, high fat group and observation group, with 10 rats in each group.The rats were fed with high fat diet for 18 weeks to induce NAFLD models.Then all the rats were sacrificed,and the serum levels of blood lipid and liver function related indexes including TC, TG, AST, ALT,HDL and LDL were detected,at the same time, the expression levels of FXR and SHP and SREBP-1c mRNA were measured.Results Among the 3 groups, the degree of liver lesions in high fat group was the severest,which in blank control group was the slightest.The fatty pathological changes, severity of inflammation and fibrosis lesion scores in observation group were (297 ±0.18) points, (1.29 ±0.27) points and (0.05 ±0.02) points,respectively,which were located between the other two groups.The serum levels of TC,ALT, AST and LDL in high fat group were significantly increased,as compared with those in blank control group and observation group, moreover, the increase degree in high fat group was more obvious (P<0.05).The expression levels of FXR, SHP and SREBP-1c mRNA in blank control group were (0.92 ±0.42)β-actin, (1.01 ±0.60)β-actin,(0.68 ±0.27)β-actin,respectively,which were significantly higher than those in high fat group ( P <0.05).The expression levels of FXR, SHP mRNA in observation group were (0.28 ±0.13)β-actin and (0.42 ±0.23)β-actin,respectively,there were significant differences between observation group and the other two groups ( P <0.05 ) . However the expression levels of SREBP-1c mRNA in observation group were (0.68 ±0.22)β-actin, there were no significant differences between observation group and blank control group ( P >0.05 ) .Conclusion The probucol has certain preventive effects on NAFLD in rats induced by high fat diet,which can obviously relieve liver fatty degeneration of rats,and the action mechanism may be correlated to the enhancement of antioxidation ability of rats to reduce the incidence rate of tissue lesion caused by oxidative stress.