摘要
目的:研究桑寄生醇提物改善2型糖尿病(T2DM)模型小鼠血糖水平及其肝肾并发症的作用及机制。方法:通过高糖高脂饲料喂养结合腹腔注射链脲佐菌素的方法建立小鼠T2DM模型。将T2DM模型小鼠60只随机分为模型对照组(生理盐水)、阳性对照组[二甲双胍,150 mg/(kg·d)]和桑寄生醇提物高、中、低剂量组[30、15、7.5 g/(kg·d),以生药量计],每组12只;另设正常小鼠12只为空白对照组(生理盐水)。连续给予小鼠相应药液或生理盐水28 d后,检测其血清中空腹血糖(FBG)、空腹胰岛素(FINS)、白细胞介素2(IL-2)、IL-4、IL-12、γ干扰素(IFN-γ)、血肌酐(Scr)、尿素氮(BUN)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的水平,收集其24 h尿液并检测尿肌酐(Ucr)水平,并计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR);采用苏木精-伊红染色法,观察肝细胞病理学变化;检测肝组织中Bcl-2、Bax水平,以及肾组织中Toll样受体4(TLR4)、核因子κB亚基p65亲和肽(NF-κB p65)水平。结果:与空白对照组比较,模型对照组小鼠的血清FBG、FINS、IL-4、ALT、AST、BUN、Scr水平及HOMA-IR值均显著升高,Ucr、IL-2、IL-12、IFN-γ水平及ISI值均显著降低(P<0.01);肝组织细胞表现出明显病理变化;肝组织中Bcl-2水平及Bcl-2/Bax比值均显著降低,Bax水平显著升高(P<0.01);肾组织中TLR4、NF-κB p65水平均显著升高(P<0.01)。与模型对照组比较,桑寄生醇提物各剂量组的肝组织病理学变化明显减轻;除桑寄生醇提物低剂量组血清中IFN-γ水平和肾组织中NF-κB p65水平无显著差异外,上述其余各指标均显著改善(P<0.01或P<0.05)。结论:桑寄生醇提物具有改善T2DM模型小鼠高血糖水平及肝肾并发症、保护肝肾功能的作用;其机制可能与提高免疫功能、上调抗凋亡相关因子、下调促凋亡及促炎相关因子的表达,从而维持肝细胞功能状态、减轻肾细胞受损程度有关。
OBJECTIVE:To study improvement effects of ethanol extract from Taxillus sutchuenensis on blood glucose level,liver and renal complications in type 2 diabetes mellitus(T2DM)model mice and its mechanism.METHODS:T2DM model was established by high-glucose and high-fat feed combined with intraperitoneal injection of streptozotocin.Totally 60 T2DM model mice were randomly divided into model control group(normal saline),positive control group[metformin,150 mg/(kg·d)]and T.sutchuenensis ethanol extract high-dose,medium-dose and low-dose groups[30,15,7.5 g/(kg·d),by crude drug],with 12 mice in each group.Other 12 normal mice were included in blank control group(normal saline).After given drug solution or normal saline for consecutive 28 d,the serum levels of FBG,FINS,IL-2,IL-4,IL-12,IFN-γ,Scr,BUN,ALT and AST were detected;24 h urine was collected to detect the Ucr levels.The insulin sensitivity index(ISI)and insulin resistance index(HOMA-IR)were calculated.HE staining was used to observe the pathological change of hepatocytes.The levels of Bcl-2 and Bax in liver tissue as well as the levels of TLR4 and NF-κB p65 in renal tissue were detected.RESULTS:Compared with blank control group,the serum levels of FBG,FINS,IL-4,ALT,AST,BUN,Scr and HOMA-IR value were increased significantly in model control group,while the levels of Ucr,IL-2,IL-12,IFN-γand ISI value were decreased significantly(P<0.01).The hepatocytes showed obvious pathological changes.Bcl-2 level and Bcl-2/Bax of liver tissue were decreased significantly,while Bax level was increased significantly(P<0.01).The levels of TLR4 and NF-κB p65 in renal tissue were increased significantly(P<0.01).Compared with model control group,histopathological changes of liver were relieved significantly in T.sutchuenensis ethanol extract groups.Except that there was no significant difference in serum level of IFN-γand level of NF-κB p65 in renal tissue in T.sutchuenensis ethanol extract low-dose group,other indexes were improved significantly(P<0.01 or P<0.05).CONCLUSIONS:T.sutchuenensis ethanol extract can improve high blood glucose,liver and renal complications,and protect liver and renal function in T2DM model mice.The mechanism may be associated with improving immunofunction,up-regulating anti-apoptosis factors,down-regulating the expression of apoptosis-promoting and inflammationpromoting factors so as to maintain the functional status of hepatocytes and reduce the degree of renal cell damage.
作者
罗泽萍
李丽
潘立卫
赖红芳
LUO Zeping;LI Li;PAN Liwei;LAI Hongfang(College of Chemical and Biological Engineering,Hechi University,Guangxi Hechi 546300,China;College of Pharmacy,Guangxi University of TCM,Nanning 530200,China)
出处
《中国药房》
CAS
北大核心
2019年第6期796-801,共6页
China Pharmacy
基金
广西自然科学基金项目(No.2017GXNSFAA198118)
广西高校中青年教师基础能力提升项目(No.2017KY0581)
河池学院2018年高层次人才科研启动费项目(No.XJ2018GKQ012)
关键词
桑寄生
醇提物
2型糖尿病
并发症
肝损伤
肾损伤
小鼠
Taxillus sutchuenensis
Ethanol extract
Type 2 diabetes mellitus
Complication
Liver injury
Renal injury
Mice
