三七总皂苷对非酒精性脂肪肝大鼠的改善作用及对NO/iNOS/NF-κB通路的影响  

Effects of Panax notoginseng total saponins on improving nonalcoholic fatty liver disease rats and NO/iNOS/NF-κB signaling pathway

作　　者：冯晓异 何朋伦 赵微 姚政 陈文慧 FENG Xiao-yi;HE Peng-lun;ZHAO Wei;YAO Zheng;CHEN Wen-hui(Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学,云南昆明650500

出　　处：《中成药》2021年第1期50-55,共6页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金(81160492,81760818);云南省应用基础研究计划项目-中医联合专项[2017FF11(-013)]。

摘　　要：目的研究三七总皂苷对非酒精性脂肪肝大鼠的改善作用及对NO/iNOS/NF-κB通路的影响。方法96只雄性SD大鼠随机分为空白组,模型组,辛伐他汀组(2 mg/kg),三七总皂苷低、中、高剂量组(4.5、9、18 mg/kg),每组16只,灌胃给药(10 mL/kg),分别于第8、12周取材,检测2个时间点各组大鼠外周血丙氨酸转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)和肝脏NO、iNOS(诱导型一氧化氮合酶);HE染色观察肝组织病理学形态;免疫组化法检测iNOS在肝脏细胞中的表达情况;Western blot法检测NF-κB(核因子-κB)、p-NF-κB(磷酸化核因子-κB)、IKKα(IκB激酶-α)、p-IKKα(磷酸化IκB激酶-α)、IκBa蛋白表达量。结果与模型组比较,给药8周后,大鼠血清各项生化指标均出现了显著下降(P<0.05);给药12周后,与第8周结果比较,模型组血清生化指标显著增加(P<0.05),而给药组增加趋势并不显著,且三七总皂苷给药剂量在抑制非酒精性脂肪肝大鼠肝脏脂质沉积方面存在剂量-效应关系。三七总皂苷可显著下调肝组织中NO、iNOS水平及NF-κB信号通路蛋白的表达量(P<0.05)。结论三七总皂苷可有效降低非酒精性脂肪肝大鼠转氨酶水平及血脂指标,同时可以抑制NO/iNOS/NF-κB信号通路,减少肝损伤,是三七总皂苷降脂护肝、减轻炎症反应的可能机制之一。AIM To study the effects of Panax notoginseng total saponins on improving nonalcoholic fatty liver disease rats and NO/iNOS/NF-κB signaling pathway.METHODS Ninety-six male SD rats were randomly divided into six groups with 16 in each group,containing normal group,model group,simvastatin group(2 mg/kg),Panax notoginseng total saponins groups(4.5 mg/kg,9 mg/kg,18 mg/kg).The normal group and model group were both administrated with 10 mL/kg normal saline for 12 weeks.After 8 weeks and 12 weeks of corresponding intervention,the rats had their levels of ALT,AST,TC,TG,LDL in peripheral blood determined;their pathological changes observed by HE staining;their iNOS expression determined by immunohistochemical staining;their expressions of NF-κB,p-NF-κB,IKKα,p-IKKαand IκBαdetermined by Western blot.RESULTS After 8 weeks of administration,the levels of serum biochemical indexes in each group were decreased significantly compared with those of the model group(P<0.05),but were not significantly varied compared with those of the normal group.In contrast to the results of the 8 weeks,12 weeks administration resulted in significantly increased serum biochemical indexes levels in the model group(P<0.05),but not in the Panax notoginseng total saponins group which shared a positive Panax notoginseng total saponins dosage-reduction of liver lipid deposition dependent relationship in the nonalcoholic fatty liver disease rats.Panax notoginseng total saponins significantly reduced the expression of NO,iNOS,NF-κB and p-NF-κB in the liver tissue(P<0.05).CONCLUSION Panax notoginseng total saponins can not only effectively reduce the levels of transaminase and blood lipid index of nonalcoholic fatty liver disease rats,but also regulate the NO/iNOS/NF-κB signaling pathway,and thus reduces liver damage.And this may be the underlying mechanism for Panax notoginseng total saponins in reducing lipidation and inflammatory reaction,and protecting liver.

关 键 词：三七总皂苷 非酒精性脂肪肝 炎症 INOS NF-ΚB 

分 类 号：R285.5[医药卫生—中药学]