姜黄对大鼠脂肪性肝炎的影响及其对PPAR-γ及IL-6、HMGB1关系的研究

Effect of turmeric on nonalcoholic steatohepatitis induced by high fat diet combined CCl_4 and the relationship with PPAR-γ,IL-6 and HMGB1

目的研究姜黄提取物对高脂饮食和CCL_4联合致大鼠脂肪性肝炎治疗作用及初步机制研究。方法 60只SD雄性大鼠随机分为6组:正常组、模型组、阳性药组、姜黄低剂量组、中剂量组和高剂量组,模型组饲喂高脂饲料,并且腹腔注射CCL_4(oil∶CCL_4=50∶50);治疗组分别给予姜黄提取物低剂量50 mg/kg,中剂量100 mg/kg,高剂量200 mg/kg,阳性药组给予复方蛋氨酸胆碱片(东宝肝泰)162 mg/kg。给药6周后取动物血清,酶标仪法检测血清中谷丙转氨酶(ALT),谷草转氨酶(AST),甘油三酯(TG),胆固醇(TC),高密度脂蛋白(HDL),低密度脂蛋白(LDL)及肝组织中羟脯氨酸(Hyp);部分肝组织石蜡包埋后做HE、Masson染色,显微镜下观察肝组织病理切片;酶联免疫法检测白细胞介素6(IL-6),高迁移率族蛋白1(HMGB1);RT-PCR检测PPAR-γ,做组织PPAR-γ免疫组化病理检查。结果治疗组与模型组相比,ALT,AST,Hyp,IL-6,HMGB1水平显著降低(P<0.05),PPAR-γ表达增加。结论姜黄提取物可治疗由高脂饮食联合CCL_4致大鼠脂肪性肝炎,治疗作用机制主要可能是通过调控PPAR-γ信号通路,促进脂质代谢;另一方面通过降低IL-6、HMGB1的表达来减轻炎症,缓解肝纤维化,从而治疗非酒精性脂肪性肝炎。

Objective To explore the anti- nonalcoholic steatohepatitis effect and its mechanism of the turmeric extract for the nonalcoholic steatohepatitis rat induced by high fat diet（ HFD） combined CCl4. Methods 60 male SD rats were randomized into 6 groups： normal group,model group,positive group,low dose group,medium dose group,and high dose group. Model group（ n = 10） rats were fed with HFD and given CCL4（ oil∶CCL4= 50∶50）,the treatment group included the low dose of turmeric extract（ 50 mg / kg）,medium dose（ 100 mg / kg）,and high dose（ 200 mg / kg）,positive group（ Compound Methionine and Choline Bitartrate Tablets） was given 162 mg / kg. After orally administrated by gavage for 6 weeks,serum Alanine transaminase（ ALT）,Aspertate Aminotransferase（ AST） and liver hydroxyproline（ Hyp） were detected,and portions of liver tissues were excised and fixed in 4% paraformaldehyde solution,and stained with hematoxylin and eosin. And then liver tissue pathology biopsy were then evaluated by microscope. To investigate the mechanism of turmeric extract on liver steatohepatitis,serum interleukin-6（ IL-6）,high mobility group protein 1（ HMGB1） by ELISA and PPAR-γ were detected. Results Compared with model group,ALT,AST and Hyp,IL-6,HMGB1 levels significantly decreased（ P〈0. 05）,and the expression of PPAR-γ significantly elevated in treatment group. Conclusion Turmeric extract can inhibit HFD combined CCl4-induced nonalcoholic steatohepatitis in rats by elevating the expression of PPAR-γ to promote lipid metabolism,on other hand,inflammation is inhibited and liver fibrosis is alleviated by reducing the levels of IL-6,HMGB1.