阳和通脉丸调控HMGB1/TLR4通路改善糖尿病下肢动脉硬化闭塞症大鼠动脉炎症OA
Yanghe Tongmai Pill Improves Arterial Inflammation in Rats with Diabetic Lower Limb Arteriosclerosis Obliterans by Regulating HMGB1/TLR4 Pathway
目的:基于 HMGB1/TLR4 信号通路,探究阳和通脉丸对糖尿病下肢动脉硬化闭塞症大鼠动脉炎症的影响.方法:将 SD 大鼠随机分对照组、模型组、阳性药物贝前列素钠组、阳和通脉丸低、中、高剂量组,每组8 只.通过高脂高糖饲养、链脲佐菌素注射及股动脉结扎构建糖尿病下肢动脉硬化闭塞症大鼠模型.HE 染色检测动脉血管、胫骨前肌组织的病理学变化,ELISA 检测血清中一氧化氮(NO)、内皮素-1(ET-1)、IL-6、IL-1β、TNF-α 的水平,免疫组织化学染色实验检测动脉血管组织中 HMGB1的水平与定位,Western blot 检测动脉血管组织中 HMGB1、TLR4、p-NF-κB p65/NF-κB p65 蛋白的表达.结果:相对于对照组,模型组大鼠动脉血管、胫骨前肌组织呈现明显的病理学损伤,血清中 NO 水平降低(P<0.05),血清中 ET-1、IL-6、IL-1β、TNF-α 水平升高(P<0.05),动脉血管组织中 HMGB1、TLR4、p-NF-κB p65/NF-κB p65 升高(P<0.05);相对于模型组,阳性药物组、阳和通脉丸低、中、高剂量组大鼠动脉血管、胫骨前肌组织的病理学损伤减轻,血清中 NO 水平升高(P<0.05),血清中 ET-1、IL-6、IL-1β、TNF-α 水平降低(P<0.05),动脉血管组织中 HMGB1、TLR4、p-NF-κB p65/NF-κB p65 降低(P<0.05),且阳和通脉丸的作用呈剂量依赖性(P<0.05).高剂量阳和通脉丸的效果优于阳性药物(P<0.05).结论:阳和通脉丸可能通过抑制动脉炎症来减轻大鼠的糖尿病下肢动脉硬化闭塞症,其机制可能与抑制 HMGB1/TLR4 信号通路相关.
Objective:To explore the effect of Yanghe Tongmai pill on arterial inflammation in rats with diabetic lower limb arteriosclerosis obliterans,based on regulating the HMGB1/TLR4 signaling pathway.Methods:SD rats were randomly divided into control group,model group,positive drug beprost sodium group,and low-,medium-,and high-dose Yanghe Tongmai pill groups,with 8 rats in each group.A rat model of diabetic lower extremity arteriosclerosis obliterans was constructed by high-fat and high-sugar diet,streptozotocin injection and femoral artery ligation.HE staining was used to detect pathological changes in ar-terial vascular and tibialis anterior muscle tissues.The levels of nitric oxide(NO),endothelin-1(ET-1),IL-6,IL-1β and TNF-α in serum were detected by ELISA.Immunohistochemical staining was used to detect the level and localization of HMGB1 in arterial vascular tissues.Western blot was used to detect the protein expression of HMGB1,TLR4 and p-NF-κB p65/NF-κB p65 in arterial vascular tissues.Results:Compared with the control group,the arterial vascular and tibialis anterior muscle tissue of the rats in the model group showed obvious pathological damage,and the NO level in serum decreased whereas the levels of ET-1,IL-6,IL-1β,TNF-α increased(P<0.05),and the expression of HMGB1,TLR4,p-NF-κB p65/NF-κB p65 in arterial vascular tissue increased(P<0.05).Compared with the model group,the pathological damage of ar-terial vascular and tibialis anterior muscle tissues reduced in the positive drug group,low-,medium-and high-dose groups of Yanghe Tongmai pills,and the NO level in serum increased whereas the levels of ET-1,IL-6,IL-1β,TNF-α decreased(P<0.05),and the expression of HMGB1,TLR4,p-NF-κB p65/NF-κB p65 in arterial vascular tissue decreased(P<0.05).Moreover,the effects of Yanghe Tongmai pills were dose-dependent.The effect of high-dose Yanghe Tongmai Pill was better than that of positive drug(P<0.05).Conclusion:Yanghe Tongmai pill may alleviate arteriosclerosis obliterans of diabetic lower extremities in rats by inhibiting arterial inflammation,and the mechanism may be related to inhibition of HMGB1/TLR4 signaling pathway.
孔五宝;陈广先;吴进;刘超;牛跃龙
河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000
糖尿病下肢动脉硬化闭塞症阳和通脉丸HMGB1/TLR4 信号通路炎 症内皮功能
Diabetic lower limb arteriosclerosis obliteransYanghe tongmai pillHMGB1/TLR4 signaling pathwayInflammationEndothelial function
《河北医学》 2026 (5)
758-764,7
河北省中医药管理局科研计划项目(编号:2022260)
评论