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不同治疗方法及中药典型方剂对脂肪肝大鼠枯否细胞 c-Jun N-末端激酶激活的影响

Effects of different therapeutic methods and typical recipes of Chinese medicine on activation of c-Jun N-terminal kinase in kupffer cells of rats with fatty liver disease.

机构信息

Department of Traditional Chinese Medicine, Medical College, Jinan University, Guangzhou 510632, China.

出版信息

Chin J Integr Med. 2012 Oct;18(10):769-74. doi: 10.1007/s11655-011-0691-5. Epub 2012 Sep 11.

Abstract

OBJECTIVE

To observe the effects of different therapeutic methods and the recipes of Chinese medicine (CM) on the activation of c-Jun N-terminal kinase (JNK) in Kupffer cells of rats with fatty liver disease and to explore the mechanisms of these therapeutic methods.

METHODS

By using a random number table, 98 rats were randomly divided into 7 groups: control group, model group, and 5 treatment groups, including soothing Liver (Gan) recipe group, invigorating Spleen (Pi) recipe group, dispelling dampness recipe group, promoting blood recipe group, and complex recipe group. Rats in the control group were fed with normal food and distilled water by gastric perfusion, while rats in the model group were fed with high-fat food and distilled spirits by gastric perfusion. Rats in the 5 treatment groups were fed with high-fat food and corresponding recipes by gastric perfusion. Twelve weeks later, all rats were sacrificed and liver tissues were stained for pathohistological observation. Kupffer cells were isolated from livers of rats to evaluate JNK and phospho-JNK expressions by Western blotting.

RESULTS

The grade of hepatic steatosis was higher in the model group than the control group (P<0.05). Compared with the model group, the grade of fatty degeneration in soothing Liver recipe group and invigorating Spleen recipe group were significantly ameliorated (P<0.05). Expressions of JNK and phospho-JNK in Kupffer cells were significantly higher in the model group than those in the control group (P<0.05, P<0.01). Compared with the model group, expressions of JNK in all treatment groups decreased, especially in invigorating Spleen recipe group and promoting blood recipe group (P<0.05). Compared with the model group, expressions of phospho-JNK in all treatment groups declined significantly (P<0.01), especially in soothing Live recipe group and invigorating Spleen recipe group.

CONCLUSIONS

The high expressions of JNK and phospho-JNK in Kupffer cells might play an important role in the pathogenesis of fatty liver disease in rats. The recipes of CM, especially invigorating Spleen recipe and soothing Liver recipe, might protect liver against injury by reducing the total JNK protein content and inhibiting the activation of JNK protein in Kupffer cells of fatty liver model rats, which showed beneficial effects on fatty liver disease.

摘要

目的

观察不同治法和中药方剂对脂肪肝大鼠枯否细胞(Kupffer 细胞) c-Jun N-末端激酶(JNK)激活的影响,探讨其作用机制。

方法

采用随机数字表法,将 98 只大鼠随机分为 7 组:正常对照组、模型组和 5 个治疗组,即柔肝方组、健脾方组、祛湿方组、活血方组和复方组。正常对照组给予普通饲料和蒸馏水灌胃,模型组给予高脂饲料和蒸馏水灌胃,5 个治疗组给予高脂饲料和相应的中药方剂灌胃。12 周后处死大鼠,肝组织病理染色观察,Western blot 法检测大鼠肝组织中 JNK 和磷酸化 JNK(p-JNK)的表达。

结果

模型组大鼠的肝脂肪变性程度高于正常对照组(P<0.05);柔肝方组和健脾方组的肝脂肪变性程度明显改善(P<0.05)。与模型组比较,各治疗组的 JNK 和 p-JNK 表达均降低(P<0.05,P<0.01),尤以健脾方组和活血方组更为明显。

结论

Kupffer 细胞 JNK 和 p-JNK 的高表达可能在大鼠脂肪肝的发病机制中起重要作用。中药方剂,尤其是健脾方和柔肝方,可能通过降低总 JNK 蛋白含量和抑制 Kupffer 细胞 JNK 蛋白的激活,减轻肝损伤,对脂肪肝发挥有益作用。

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