参芪复方调控GK大鼠大血管病变PTEN/PI3K通路的实验研究

作者	单位
刘桠	成都中医药大学
谢春光	成都中医药大学
陈敏	成都中医药大学
庄灿	成都中医药大学
高泓	成都中医药大学

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中文摘要:

目的探讨参芪复方对Goto-Kakizaki(GK)大鼠2型糖尿病大血管病变的PTEN/PI3K通路与血管新生的影响及作用机制。方法选择血糖≥11.1mmol/L的GK大鼠随机分为GK组、模型组、西药[阿托伐他汀1.6mg/(kg·d)]组、中药[参芪复方1.44g/(kg·d)]组,另设正常Wistar对照组。模型、西药、中药组每天给予Nω-硝基-L-精氨酸甲酯(L-NAME)0.1mg/mL,加入饮用水中进行造模。Wistar组喂饲普通饲料,其余各组喂饲高脂饲料,时间为35天。造模同时开始给予相应受试药物,周期35天。实验结束时,腹主动脉采血,冰上取主动脉;检测各组血糖、血脂水平,HE染色对腹主动脉进行形态学观察,实时荧光定量PCR技术检测主动脉PTENmRNA、PI3Kp85mRNA的表达水平。结果参芪复方能改善GK大鼠一般状态、糖脂代谢及腹主动脉形态学变化。大鼠主动脉PTENmRNA表达中药组(1.10±0.48)较GK组(0.63±0.16)、模型组(0.17±0.07)均显著升高(均P<0.01),与西药组(1.11±0.46)比较,差异无统计学意义(P>0.05);大鼠主动脉PI3Kp85mRNA表达中药组(0.19±0.05)较GK组(1.38±0.43)降低(P<0.01),分别与模型组(0.33±0.09)、西药组(0.11±0.06)比较,差异均无统计学意义(P>0.05)。结论参芪复方能增加主动脉PTENmRNA表达,抑制主动脉PI3Kp85mRNA表达,可能是参芪复方抑制血管新生、防治糖尿病大血管病变的部分作用机制。

英文摘要:

Objective To research the effects and mechanism of Shenqi compound (SQC) on PTEN/PI3K signal transducing path and angiogenesis in Goto-Kakizaki (GK) rats with diabetes mellitus type 2 (DM2) caused macroangiopathy. Method GK rats with blood sugar≥11.1 mmol/L were divided into 4 groups,the GK group,the model group,the Western medicine (WM) group treated by atorvastatin 1.5 mg/(kg·d) and the Chinese medicine (CM) group treated with SQC 1.44 g/(kg·d). All were fed 35 days with high fatty diet,but to the latter three groups,Nω-nitriyl-L-arginine methyl ester 0.1 mg/mL was added into their drinking water for macroangiopathy model establishing. Besides,a group of normal Wistar rats fed with ordinary forage was set for control. Rat’s blood glucose and lipids were measured,morphology of abdominal aorta wall tissue was observed with HE staining,and mRNA expressions of PTEN and PI3Kp85 in aortic wall were detected by Real-time PCR. Results General condition,gluco-lipid metabolism and aortic morphology in the CM group were significantly better than those in the model group. PTEN mRNA expression in the CM group (1.10±0.48) was significantly higher than that in the GK group (0.63±0.16) and the model group(0.17±0.07,both P<0.01),but near to that in the WM group (1.11±0.46),while the PI3Kp85 mRNA expression in the TCM group (0.19±0.05) was lower than that in the GK group (1.38±0.43,P<0.01),but near to that in the model group (0.33±0.09) and the WM group (0.11±0.06,both P>0.05). Conclusion SQC could increase the PTEN mRNA expression and restrain the PI3Kp85 mRNA expression in aorta,which is possibly the partial mechanisms of action of the remedy in inhibiting angiogenesis and preventing diabetic macroangiopathy.

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