甲状腺素对非酒精性脂肪肝大鼠ANGPTL3表达的影响

Effects of Thyroid Hormone on the Expression of ANGPTL3 in Nonalcoholic Fatty Liver in Rats

目的探讨甲状腺激素(TH)对非酒精性脂肪肝(NAFLD)大鼠血管生成素样蛋白3(ANGPTL3)表达的影响,明确TH是否通过ANGPTL3途径影响NAFLD大鼠肝脏脂肪变性。方法健康3周初断乳SD雄性大鼠30只,随机分为5组:正常组、高脂组、甲状腺素预防组、甲状腺素治疗组、吉非罗齐组;所有大鼠除正常组外均以高脂饮食喂养,分别于0、4、8、12周断尾取血,12周末处死大鼠,取肝脏。苏木精-伊红法(HE)染色,进行肝脂肪变性程度评分,采用酶联免疫吸附实验(ELISA法)检测血清ANGPTL3含量,逆转录聚合酶链式反应(RT-PCR)检测肝脏中ANGPTL3 mRNA的表达水平。结果甲状腺素预防组及吉非罗齐组大鼠肝组织脂肪变性程度均低于高脂组及甲状腺素治疗组(P<0.01)。高脂组血清ANGPTL3水平在第8周后出现增高,呈时间依赖性,其肝组织中的ANGPTL3 mRNA表达亦较正常对照组明显升高(P<0.01)。甲状腺预防组大鼠在8、12周均出现血清ANGPTL3浓度降低,并可下调肝脏ANGPTL3 mRNA水平,与高脂组及甲状腺素治疗组相比较,差异均具有统计学意义(P<0.05)。甲状腺素治疗组与吉非罗齐组亦可一定程度下调血清ANGPTL3水平及肝组织中ANGPTL3 mRNA表达(P<0.05),但其降低的程度少于甲状腺素预防组(P<0.05)。结论 NAFLD形成过程中伴有ANGPTL3进行性增高,早期给予小剂量TH可通过ANGPTL3途径而改善NAFLD大鼠肝脂肪变性程度。

Objective To investigate the effects of TH on the expression of ANGPTL3 of NAFLD rats, and the effect of TH on hepatic steatosis in NAFLD rats by ANGPTL3 pathway. Methods 30 SD male rats,were randomly divided into 5 groups：normal control group, high fat group, thyroxine prevention group, treatment group, gemfibrozil group; All rats were fed with high fat diet except the normal group, blood was taken out from the tail of rat at 0,4,8,12 weeks, All of them were killed at the end of 12 weeks,the degree of hepatic steatosis score was observed by HE staining of Liver pathological sec- tion. Serum ANGPTL3 content was detected by ELISA method, and the mRNA expression of ANGPTL3 in liver tissue was measured with RT-PCR. Results Rat liver steatosis degree in thyroxine prevention group and gemfibrozil group was low- er than the high fat group and thyroxine treatment（P 〈0.05）. In the high fat group,the serum level of ANGPTL3 was in- creased at 8W, the expression of ANGPTL3 mRNA in liver tissue was significantly higher than the normal control （P 〈 0. 01 ）. Thyroxine prevention group rats showed the decrease in serum concentration of ANGPTL3 at 8 weeks, 12 weeks, and lower hepatic ANGPTL3 mRNA level, compared with high cholesterol group, gemfibrozil group and thyroxine treatment groups ,was statistically significant（P 〈 0.05 ）. Thyroxine treatment group and gemfibrozil group can also in a certain degree decreasing serum ANGPTL3 level and expression of ANGPTL3 mRNA in liver tissue（P 〈 0.05 ）, but the extent of reduction is less than thyroxine prevention group（ P 〈 0.05 ）. Conclusion The formation process of NAFLD increased with AN- GPTL3,ans early administration of small dose of TH hepatic adipose degeneration in NAFLD rats improved through AN- GPTL3 pathway.