引用本文: | 赵芸慧,梁永林,朱向东,段永强,宋冰,白敏,裴晓丽,章溥.参七糖络丸调控PI3K/Akt通路改善肥胖型糖尿病小鼠肝细胞凋亡的机制研究[J].中国现代应用药学,2025,42(6):51-59. |
| zhaoyunhui,liangyonglin,ZHU Xiangdong,DUAN Yongqiang,SONG Bing,BAI Min,PEI Xiaoli,ZHANG Pu.Effect of Shenqitangluo wan on PI3K/Akt pathway on hepatocyte apoptosis in obese diabetic mice[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(6):51-59. |
|
|
|
本文已被:浏览 44次 下载 29次 |
 码上扫一扫! |
|
参七糖络丸调控PI3K/Akt通路改善肥胖型糖尿病小鼠肝细胞凋亡的机制研究 |
赵芸慧1, 梁永林1, 朱向东2, 段永强2, 宋冰1, 白敏1, 裴晓丽1, 章溥1
|
1.甘肃中医药大学;2.宁夏医科大学
|
|
摘要: |
目的:探讨参七糖络丸调控PI3K/Akt通路改善肥胖型糖尿病肝脏细胞凋亡的作用及机制。方法:将60只SPF级7周龄db/db小鼠纳入实验,随机分为模型组、阳性对照组和参七糖络丸高、中、低剂量组,另选12只同龄db/m小鼠作为空白对照组。阳性对照组每日给予二甲双胍(0.26g/Kg)灌胃,参七糖络丸高、中、低剂量组每日分别给予不同浓度参七糖络丸(76 g/Kg, 38 g/Kg, 19 g/Kg)灌胃,空白对照组和模型组每日给予等量蒸馏水灌胃,持续干预8周。观察小鼠生存状态并测定体质量、空腹血糖(FBG);采用生化试剂盒检测肝脏AST、ALT含量;采用苏木精-伊红(HE)染色、油红O(Oil red)染色和TUNEL染色法观察各组肝脏组织病理变化、脂肪堆积及凋亡情况;采用免疫组织化学染色(IHC)法分析肝脏组织中Bax、Bcl-2蛋白表达水平;蛋白免疫印迹法(WB)检测各组小鼠肝组织中PI3K、p-Akt、Caspase-3蛋白表达水平。结果:与空白组相比,模型组小鼠体质量明显升高(P<0.05);FBG显著升高(P<0.05);肝组织中AST、ALT显著增高(P<0.05);肝脏病理及油红O染色显示肝脏脂肪变性程度显著增加,肝细胞结构紊乱;肝脏细胞凋亡率显著升高(P<0.05);肝脏组织中Caspase-3、Bax蛋白表达水平显著升高(P<0.05);PI3K、p-Akt、Bcl-2蛋白表达水平显著降低(P<0.05);Bax/Bcl-2显著升高(P<0.05)。与模型组相比,参七糖络丸高、中剂量组小鼠体质量明显降低(P<0.05);FBG显著降低(P<0.05);肝脏细胞凋亡率显著降低(P<0.05);治疗后各组小鼠的肝脏结构损伤程度明显减轻,脂肪变性程度有所减轻;肝组织中AST、ALT显著降低(P<0.05);肝脏组织中Bax、Caspase-3表达水平显著降低(P<0.05);PI3K、p-Akt、Bcl-2表达水平显著升高(P<0.05);Bax/Bcl-2显著降低(P<0.05)。结论:参七糖络丸可以改善肥胖型糖尿病小鼠血糖及肝脏脂肪变性,其作用机制可能与调节PI3K/Akt通路抑制肝细胞凋亡有关。 |
关键词: 肥胖型糖尿病 参七糖络丸 细胞凋亡 肝脏脂肪变性 PI3K/Akt通路 |
DOI: |
分类号: |
基金项目:宁夏回族自治区重点研发重点项目(2022BEG02034);宁夏回族自治区重点研发计划项目引才专项(2022YCZX0104) |
|
Effect of Shenqitangluo wan on PI3K/Akt pathway on hepatocyte apoptosis in obese diabetic mice |
zhaoyunhui1, liangyonglin1, ZHU Xiangdong2, DUAN Yongqiang2, SONG Bing1, BAI Min1, PEI Xiaoli1, ZHANG Pu1
|
1.Gansu University Of Chinese Medicine;2.Ningxia Medical Univercity
|
Abstract: |
Objective: To investigate the effect and mechanism of Shenqitangluo wan on improving apoptosis of liver cells in obese diabetes mellitus by regulating PI3K/Akt pathway. Methods: 60 SPF grade 7-week-old db/db mice were included in the experiment and randomly divided into model group, positive control group and Shenqitangluo wan high-dose, medium-dose and low-dose groups. 12 db/m mice of the same age were selected as blank control group. Positive control group was given metformin (0.26g/Kg) by gavage, Shenqitangluo wan high, medium and low dose groups were given different concentrations of Shenqitangluo wan (76 g/Kg, 38 g/Kg, 19 g/Kg) by gavage, blank control group and model control group were given the same amount of distilled water by gavage every day, and the intervention lasted for 8 weeks. The living state of the mice was observed and body weight and fasting blood glucose (FBG) were measured. The contents of AST and ALT in liver were detected by biochemical kit. Hematoxylin-eosin (HE), Oil red (O) and TUNEL staining were used to observe the pathological changes, fat accumulation and apoptosis of liver tissues in each group. The expression levels of Bax and Bcl-2 protein in liver tissues were analyzed by immunohistochemical staining (IHC). The expression level of PI3K/ p-Akt/Caspase-3 protein in liver tissues of mice in each group was detected by protein immunoprinting (WB). Results: Compared with blank group, the body weight of mice in model group was significantly increased (P<0.05). FBG was significantly increased (P<0.05); AST and ALT in liver tissue were significantly increased (P<0.05). Liver pathology and oil red O staining showed that the degree of liver steatosis increased significantly and the structure of liver cells was disordered. The apoptosis rate of liver cells was significantly increased (P<0.05). The expression levels of PI3K, P-Akt, Caspase-3 and Bax in liver tissues were significantly increased (P<0.05). The expression level of Bcl-2 protein was significantly decreased (P<0.05). Bax/Bcl-2 was significantly increased (P<0.05). Compared with model group, the body weight of mice in Shenqitangluo wan high-dose and medium-dose groups decreased significantly (P<0.05). FBG was significantly decreased (P<0.05); The apoptosis rate of liver cells was significantly decreased (P<0.05). After treatment, the damage degree of liver structure and the degree of steatosis of mice in each group were significantly reduced. AST and ALT in liver tissue were significantly decreased (P<0.05). The expression levels of PI3K, P-Akt, Bax and Caspase-3 in liver tissues were significantly decreased (P<0.05). The expression level of Bcl-2 was significantly increased (P<0.05); Bax/Bcl-2 was significantly decreased (P<0.05). Conclusion:Shenqitanglu wan can improve blood sugar and liver steatosis in mice with obesity diabetes mellitus, and its mechanism may be related to regulating PI3K/Akt pathway and inhibiting hepatocyte apoptosis. |
Key words: obese diabetes mellitus Shenqi Tangluo wan Cell apoptosis Hepatic steatosis PI3K/Akt pathway |
|
|
|
|