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黄芪桂枝五物汤对糖尿病性下肢动脉硬化闭塞症大鼠动脉炎症的作用及其机制研究
王培宇,贾振,赵钢
0
黑龙江中医药大学黑龙江哈尔滨150000;黑龙江中医药大学附属第一医院黑龙江哈尔滨150000
摘要:
目的 研究黄芪桂枝五物汤对糖尿病性下肢动脉硬化闭塞症大鼠的治疗作用及其机制。方法:将48 只健康雄性SD大鼠随机分为模型组、低剂量中药组、高剂量中药组和空白对照组,每组12 只,低剂量中药组和高剂量中药组分别给予1 倍和2 倍等效剂量中药汤剂灌胃,模型组和空白对照组给予生理盐水灌胃,连续干预4 周。末次给药后24 h,观察大鼠一般情况、体质量、血糖水平,酶联免疫吸附法检测血清肿瘤坏死因子-琢(TNF-琢)、白细胞介素-16(IL-16)、一氧化氮(NO)、内皮素-1(ET-1)水平,观察腓肠肌新生血管密度,HE 染色观察动脉血管病理变化,免疫印迹法检测缺氧诱导因子-1琢(HIF-1琢)/血管内皮生长因子(VEGF)通路蛋白表达水平。结果:低剂量中药组、高剂量中药组及模型组大鼠较空白对照组精神状态差,活跃性减弱,血糖升高,血清炎症因子水平升高,血管内皮功能受损。与模型组比较,低剂量中药组大鼠精神状态更好,行动较活跃,血糖下降,血清炎症因子水平降低,内皮细胞功能更完善,腓肠肌组织新生血管密度更高,HIF-1琢及VEGF 蛋白表达水平更高(p<0.05)。与低剂量中药组比较,高剂量中药组大鼠血糖下降,血清炎症因子水平降低,NO 水平无显著差异,ET-1 水平下降,腓肠肌组织新生血管密度更高,VEGF 蛋白表达水平更高(p<0.05)。结论:黄芪桂枝五物汤可能通过调节HIF-1琢/VEGF 信号通路而抑制局部炎症反应,改善内皮细胞功能,从而起到治疗糖尿病性下肢动脉硬化闭塞症的作用。
关键词:  黄芪桂枝五物汤  下肢动脉硬化闭塞症  缺氧诱导因子  血管内皮生长因子
DOI:10.3969/j.issn.1007-6948.2025.01.022
投稿时间:2024-07-10
基金项目:黑龙江省中医药科研项目(ZHY2022-159)
Effects and mechanism of Huangqi Guizhi Wuwu decoction on arterial inflammation in rats with diabetes induced lower extremity atherosclerotic occlusion
WANG Pei-yu,JIA Zhen,ZHAO Gang
Abstract:
Objective To observe the therapeutic mechanism of Huangqi Guizhi Wuwu decoction on diabetic lower extremity arteriosclerosis obliterans in rats. Methods A total of 48 experimental rats were randomly assigned to four groups: model, low-dose traditional Chinese medicine, high-dose traditional Chinese medicine, and blank control, each consisting of 12 rats. The low -dose and high -dose traditional Chinese medicine groups received 1 and 2 times equivalent doses of traditional Chinese medicine decoction by gavage,respectively, whereas the model and blank control groups got normal saline by gavage for 4 weeks. The rats'overall conditions, body weight, and blood glucose levels were assessed 24 hours after their previous injection.Serum levels of TNF-a, IL-16, NO and ET-1 were measured using ELISA. We assessed the density of new blood vessels in the gastrocnemius muscle, examined arterial pathological alterations using HE staining, and detected protein expression levels of the HIF -1琢/VEGF pathway using Western blotting. Results In comparison to the blank control group, rats in the low-dose Chinese medicine group, high-dose Chinese medicine group, and model group had a lower mental state, decreased activity, increased blood sugar, elevated serum inflammatory markers, and impaired vascular endothelial function. Compared to the model group, rats in the lowdose Chinese medicine group had better mental state, more active actions, lower blood sugar, lower serum inflammatory factors, more perfect endothelial cell function, higher density of new blood vessels ingastrocnemius, and higher expression levels of HIF-1a and VEGF proteins (p<0.05). Compared to the low-dose Chinese medicine group, the high-dose Chinese group showed lower blood sugar, serum inflammatory markers, NO level, ET-1 level, higher density of new blood vessels in gastrocnemius, and higher expression level of VEGF protein (p<0.05). Conclusion Huangqi Guizhi Wuwu decoction may help cure diabetic arteriosclerosis obliterans in the lower limbs by modulating the HIF -1a/VEGF signal pathway, decreasing local inflammation, and increasing endothelial cell function.
Key words:  Huangqi Guizhi Wuwu decoction  diabetic lower limb arteriosclerosis obliterans  VEGF  HIF-1a

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