益肝解毒方及其拆方对非酒精性脂肪性肝炎大鼠UCP-2的影响

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摘要目的通过高脂饮食建立非酒精性脂肪性肝炎（NASH）大鼠模型，观察益肝解毒方及其拆方对NASH大鼠UCP-2的影响。方法将60只Wistar大鼠依据随机数字表法分为正常组、模型组、全方组、化痰组、祛瘀组、解毒组，每组10只，给予高脂饲料喂养16周以复制NASH模型，正常组（生理盐水1.575 mL/100 g灌胃）、模型组（生理盐水1.575 mL/100 g灌胃）、全方组（中药1.730 g/100 g灌胃）、化痰组（中药1.730 g/100 g灌胃）、祛瘀组（中药1.730 g/100 g灌胃）、解毒组（中药1.730 g/100 g灌胃）干预至16周后处死大鼠，收集标本。运用赖式比色法测定各组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、谷氨酰转移酶（GGT）、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、活性氧（ROS）；RT-PCR法检测UCP-2 mRNA；Western blot检测UCP-2蛋白。结果大鼠NASH模型成功建立。全方组及各拆方组ALT、AST、GGT、TC、TG、HDL、ROS、UCP-2 mRNA均值较模型组明显降低，LDL较模型组明显升高，差异有统计学意义（P ＜ 0.05）。各拆方组ALT、AST、GGT、TC、TG、HDL、ROS、UCP-2 mRNA均值均高于全方组，差异有统计学意义（P ＜ 0.05），祛瘀组、解毒组ALT、AST、GGT、TC、TG、HDL水平上低于化痰组，差异有统计学意义（P ＜ 0.05），祛瘀组LDL水平均高于其他各组，差异有统计学意义（P ＜ 0.05）。Western blot结果显示，与正常组比较，模型组UCP-2蛋白表达增强；与模型组比较，全方组UCP-2蛋白表达减低；各拆方组UCP-2蛋白表达相近。结论全方组效果最好，体现出中药复方是其各组成部分协同作用的结果。益肝解毒方可抑制ROS产生，降低UCP-2高表达和血清中ALT、AST、GGT、TC、TG、HDL水平，提高LDL水平。

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	郑昕1 陈骏毅2 陆仕洪3 周菲1 郭兆玮1 庄敏之1 王亚平1

关键词 ：非酒精性脂肪性肝炎, 拆方研究, 益肝解毒方, 大鼠

Abstract：Objective To establish the rat model of non-alcoholic steatohepatitis (NASH) by high-fat diet, and to observe the effect of Yigan Jiedu Decoction and its preparation on UCP-2 in rats with NASH. Methods According to the random number table method, 60 Wistar rats were divided into normal group, model group, whole formula group, phlegm elimination group, stasis removal group and detoxification group, 10 rats in each group were given high-fat diet for 16 weeks to replicate the NASH model. Rats in the normal group (1.575 mL/100 g normal saline), model group (1.575 ml/100 g normal saline), whole formnla group (1.730 g/100 g of traditional Chinese medicine), phlegm elimination group (1.730 g/100 g of traditional Chinese medicine), stasis removal group (1.730 g/100 g of traditional Chinese medicine), and detoxification group (1.730 g/100 g of traditional Chinese medicine) were put to death after 16 weeks of intervention, and specimens were collected. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transferase (GGT), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and reactive oxygen species (ROS) were determined by Reitman colorimetry. UCP-2 mRNA was detected by RT-PCR. UCP-2 protein was detected by Western blot. Results NASH model of rats was successfully established. The mean values of ALT, AST, GGT, TC, TG, HDL, ROS and UCP-2 mRNA in the whole formula group and its preparation groups were significantly lower than those in the model group, while LDL was higher than that in the model group, with statistically significant differences (P ＜ 0.05). The mean values of ALT, AST, GGT, TC, TG, HDL, ROS and UCP-2 mRNA in preparation groups were higher than those in the whole formula group, with statistically significant differences (P ＜ 0.05). The levels of ALT, AST, GGT, TC, TG and HDL in the stasis removal group and the detoxification group were lower than those in the phlegm elimination group, and the differences were statistically significant (P ＜ 0.05). The LDL level of the stasis removal group was higher than that of other groups, and the difference was statistically significant (P ＜ 0.05). The results of Western blot showed that compared with normal group, the expression of UCP-2 protein in the model group was increased; compared with model group, the expression of UCP-2 protein in the whole formula was decreased; while the expression of UCP-2 protein among all preparation groups was similar. Conclusion The whole formula group has the best effect, which shows that the TCM compound is the result of the synergistic effect of its components. Yigan Jiedu Decoction can inhibit the production of ROS, reduce the high expression of UCP-2 and the levels of serum ALT, AST, GGT, TC, TG, HDL, and improve the level of LDL.

Key words： Non-alcoholic steatohepatitis Recipe compotion Yigan Jiedu Decoction Rat

基金资助:上海市基层名老中医专家传承研究工作室建设项目（JCZYGZS-015）；
上海市虹口区卫生计划生育委员会医学科研课题（虹卫1402-04）。

通讯作者: 王亚平（1955.9-），男，主任医师；研究方向：中医肝病、慢性肝病、脾胃病。

作者简介: 郑昕（1978.2-），男，副主任医师，上海市第四人民医院中医科副主任；研究方向：中医脂肪肝病。

引用本文:

郑昕1 陈骏毅2 陆仕洪3 周菲1 郭兆玮1 庄敏之1 王亚平1. 益肝解毒方及其拆方对非酒精性脂肪性肝炎大鼠UCP-2的影响[J]. 中国医药导报, 2019, 16(20): 9-12,28.
ZHENG Xin1 CHEN Junyi2 LU Shihong3 ZHOU Fei1 GUO Zhaowei1 ZHUANG Minzhi1 WANG Yaping1. Effects of Yigan Jiedu Decoction and its preparation on UCP-2 in non-alcoholic steatohepatitis rats. 中国医药导报, 2019, 16(20): 9-12,28.

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