桑寄生醇提物改善2型糖尿病模型小鼠血糖水平及其肝肾并发症的作用及机制研究-中国药房

桑寄生醇提物改善2型糖尿病模型小鼠血糖水平及其肝肾并发症的作用及机制研究

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篇名：	桑寄生醇提物改善2型糖尿病模型小鼠血糖水平及其肝肾并发症的作用及机制研究
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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。
ABSTRACT：	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-γ and 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-γ and 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 inflammation- promoting factors so as to maintain the functional status of hepatocytes and reduce the degree of renal cell damage.
期刊：	2019年第30卷第6期
作者：	罗泽萍，李丽，潘立卫，赖红芳
AUTHORS：	LUO Zeping，LI Li，PAN Liwei，LAI Hongfang
关键字：	桑寄生；醇提物；2型糖尿病；并发症；肝损伤；肾损伤；小鼠
KEYWORDS：	Taxillus sutchuenensis； Ethanol extract； Type 2 diabetes mellitus； Complication； Liver injury； Renal injury； Mice
阅读数：	388 次
本月下载数：	5 次

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