下丘脑STAT3在非酒精性脂肪性肝病大鼠发病中的作用及降脂颗粒的干预

Effect of Jiangzhi granule on STAT3 expression in hypothalamus of rats with nonalcoholic fatty liver disease

目的:观察非酒精性脂肪肝大鼠下丘脑STAT3蛋白表达和组成性激活的改变,以及中药降脂颗粒对其干预作用.方法:高脂饲料制备非酒精性脂肪肝大鼠模型,待造模成功后将大鼠随机分为模型对照组(n=10)、辛伐他汀组(n=10)、降脂颗粒组(n=10),每日进行ig药物干预,4wk,并设空白对照组(n=8).比色法检测血清TG、TC;HE染色观察观察肝组织脂肪变和炎症;Westernblot检测下丘脑磷酸化STAT3蛋白表达,EMSA检测下丘脑STAT3的组成性激活状态.结果:磷酸化STAT3蛋白表达及其组成性激活在非酒精性脂肪肝大鼠均明显降低,降脂颗粒用药组及辛伐他汀组能下调大鼠血清TG(0.54±0.09mmol/L,0.68±0.08mmol/Lvs0.84±0.09mmol/L,均P<0.05)、TC(1.85±0.31mmol/L,2.08±0.30mmol/Lvs2.84±0.30mmol/L,均P<0.05)水平,减轻肝脂肪变(2.26±0.52,2.57±0.67vs3.10±0.57,均P<0.05)和炎症程度(0.68±0.67,0.95±0.6vs1.52±0.71,均P<0.05);上调下丘脑组织磷酸化STAT3蛋白表达及其组成性激活.结论:STAT3在非酒精性脂肪肝大鼠下丘脑组织表达和激活明显下降,中药降脂颗粒对非酒精性脂肪肝有很好的治疗作用,并可上调STAT3的表达和组成性激活.

AIM： To observe the expression and activation of hypothalamus STAT3 on rats with nonalcoholic fatty liver disease （NAFLD）, and to study therapeutically effect of Jiangzhi granule on it. METHODS： High fat-induced NAFLD rats were randomly divided into 3 groups： model group （n = 10）; Jiangzhi granule group （n = 10）; sim- vastatin group （n = 10）. Blank group were fed with chow food （n = 8）. Four weeks later, all rats were sacrificed. Liver tissue samples were then collected for pathologic analysis. Liver index, serum TG and TC were detected using colorim-etry. Phosphorylated STAT3 protein expression of hypothalamus was determined by Western blot while the activated STAT3 expression by EMSA. RESULTS： Phosphorylated STAT3 protein and activated STAT3 expression in hypothalamus were significantly lower in rats with NAFLD. Jiangzhi granule and simvastatin significantly lowered serum levels of TG （0.54 ± 0.09 mmol/L, 0.68 ± 0.08 mmol/L vs 0.84 ± 0.09 mmol/L, both P 〈 0.05）, TC （1.85 ± 0.31 mmol/L, 2.08 ± 0.30 mmol/L vs 2.84 ±0.30 mmol/L, both P 〈 0.05）, improved steotosis （2.26 ± 0.52, 2.57 ± 0.67 vs 3.10 ± 0.57, both P 〈 0.05） and relieved inflammation （0.68 ± 0.67, 0.95 ± 0.6 vs 1.52 ±0.71, both P 〈 0.05）, and up-regulated the phosphorylated and acti- vated STAT3 expression. CONCLUSION： Hypothalamus STAT3 is in- volved in the mechanism of NAFLD, Jiangzhi granule can effectively improve liver function and steatosis, and up-regulate the expression of STAT3 in hypothalamus.