哈萨克民族药柯孜木克颗粒对代谢综合征TGR5表达的调控作用  

Regulatory Effect of Kezimuke Granules on Expression of TGR5 in Metabolic Syndrome

作　　者：马丽娜·阿新拜 毛丽旦·阿扎提[2] 陈阳 库丽夏西·马尼 梅拉·哈万 阿依巴尔申·努尔拉提 兰卫[3] Malina Axinbai;Maolidan Azhati;CHEN Yang;Kulixiaxi Mani;Meila Hawan;Ayibaershen Nuerlati;LAN Wei(Department of Integrated Traditional Chinese and Western Medicine,College of Traditional Chinese Medicine,Xinjiang Medical University,Wulumuqi 830000,China;Experimental Center,College of Traditional Chinese Medicine,Xinjiang Medical University,Wulumuqi 830000,China;Department of Traditional Chinese Medicine,College of Traditional Chinese Medicine,Xinjiang Medical University,Wulumuqi 830000,China;Pharmacy of Kazakh Ethnic Medicine,Xinjiang Kazakh Medical Hospital of Altay,Altay 836300,China)

机构地区：[1]新疆医科大学中医学院中西医结合系,乌鲁木齐830000 [2]新疆医科大学中医学院实验中心,乌鲁木齐830000 [3]新疆医科大学中医学院中药系,乌鲁木齐830000 [4]新疆阿勒泰地区哈萨克医医院哈药药房,新疆阿勒泰836300

出　　处：《南昌大学学报（医学版）》2022年第5期8-13,共6页Journal of Nanchang University：Medical Sciences

基　　金：新疆维吾尔自治区自然科学基金(2018D01C152)。

摘　　要：目的探讨柯孜木克颗粒对喂养型代谢综合征大鼠肝脏组织TGR5蛋白表达的影响及改善代谢综合征的作用机制。方法将29只雄性SD大鼠随机分为正常组(n=6)、模型组(n=3)、用药组[柯孜木克颗粒低剂量组(n=6)、柯孜木克颗粒中剂量组(n=5)、柯孜木克颗粒高剂量组(n=5)和二甲双胍组(n=4)]。正常组给予普通饲料,其余各组喂养高盐高脂高糖饲料,时间为8周。8周后用药组分别给予柯孜木克颗粒[低、中、高剂量分别为17.6、35.19、70.38 mg·kg^(-1)·d^(-1)]、盐酸二甲双胍悬浊液[3 mg·kg^(-1)·d^(-1)]灌胃干预,正常组和模型组以10 mg·kg^(-1)·d^(-1)生理盐水灌胃,1次·d^(-1),连续给药4周。采用ELISA法检测动脉血肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平,HE染色观察肝组织病理形态学变化,SP法免疫组织化学检测肝脏组织TGR5蛋白的表达。结果与模型组(0.67±0.02)相比,柯孜木克颗粒低(0.57±0.07)、中(0.60±0.06)、高(0.56±0.04)剂量组血清TNF-α水平均降低,差异有统计学意义(P<0.05);二甲双胍组(0.63±0.03)血清TNF-α水平差异无统计学意义(P>0.05)。与正常组相比(186.24±0.35),模型组(180.83±4.37)TGR5平均光密度值降低(P<0.05);与模型组相比,柯孜木克颗粒低(185.85±1.14)、中(186.11±0.93)、高剂量组(187.91±0.66)及二甲双胍组(184.55±0.98)TGR5平均光密度值均升高(P<0.05)。结论柯孜木克颗粒能够通过TGR5蛋白表达的上调,降低MS模型大鼠血清TNF-α水平,进而改善MS模型大鼠肝组织病变程度。Objective To investigate the effect of Kezimuke granules on TGR5 protein expression in the liver of rats with metabolic syndrome and the mechanism of improving metabolic syndrome.Methods Twenty-nine male SD rats were randomly divided into six groups.The normal group(n=6)was given ordinary diet.The remaining rats were fed with high-salt,high-fat and high-sugar diet to establish the model of metabolic syndrome.After 8 weeks of feeding,the rats with metabolic syndrome were intragastrically treated with low-dose Kezimuke granules(17.6 mg·kg^(-1)·d^(-1),n=6),medium-dose Kezimuke granules(35.19 mg·kg^(-1)·d^(-1),n=5),high-dose Kezimuke granules(70.38 mg·kg^(-1)·d^(-1),n=5)or metformin hydrochloride suspension(3 mg·kg^(-1)·d^(-1),n=4)once per day for 4 weeks.The rats in normal group and model group(n=3)only received normal saline(10 mg·kg^(-1)·d^(-1)).The levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in arterial blood were measured by ELISA.The hepatic histopathological changes were observed by HE staining.The expression of TGR5 protein in the liver was detected by immunohistochemistry.Results Serum TNF-αlevel in the model group(0.67±0.02)was significantly higher than that in low-dose(0.57±0.07),medium-dose(0.60±0.06)or high-dose Kezimuke group(0.56±0.04)(P<0.05).There was no statistical difference in TNF-αlevel between model group and metformin group(0.63±0.03)(P>0.05).Compared with the normal group(186.24±0.35),the mean optical density value of TGR5 decreased in the model group(180.83±4.37)(P<0.05).Compared with the model group,the mean optical density value of TGR5 increased in low-dose Kezimuke group(185.85±1.14),medium-dose Kezimuke group(186.11±0.93),high-dose Kezimuke group(187.91±0.66)and metformin group(184.55±0.98)(P<0.05).Conclusion Kezimuke granules can reduce serum TNF-αlevels and alleviate hepatic lesions through upregulating TGR5 expression in rats with metabolic syndrome.

关 键 词：代谢综合征 柯孜木克颗粒 TGR5 高盐高脂高糖 动物 实验 大鼠 

分 类 号：R589[医药卫生—内分泌]