丹蛭降糖胶囊调控ASK1-JNK信号通路对糖尿病大鼠主动脉粥样硬化干预机制OA
Intervention mechanism of Danzhi Jiangtang capsule in regulating ASK1-JNK signaling pathway for atherosclerosis in aorta of diabetic rats
目的:探究丹蛭降糖胶囊对糖尿病(DM)合并动脉粥样硬化(AS)模型的 SD 大鼠主动脉凋亡信号调节激酶 1-c-Jun 氨基末端激酶(ASK1-JNK)信号通路的作用.方法:用链脲佐菌素(STZ)溶液、N-硝基-L-精氨酸甲酯(L-NAME)对 SD 大鼠构建 DM 合并 AS 模型.成功建模的大鼠随机分为模型组、阿托伐他汀组以及丹蛭降糖胶囊高剂量组 1.08 g/(kg·d)、中剂量组 0.54 g/(kg·d)和低剂量组 0.27 g/(kg·d),另设空白组,各给药组分别灌胃相应药物,模型组与空白组给予等体积 0.9%NaCl 溶液,干预 8 周后,检测相关指标.结果:与空白组比较,模型组大鼠空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)、内皮缩血管肽 1(ET-1)升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)、一氧化氮(NO)降低(均 P<0.01),主动脉 ASK1、p-ASK1、JNK、p-JNK、c-Jun 蛋白相对表达显著上调(均 P<0.01).与模型组相比,丹蛭降糖胶囊显著降低 FPG、TG、TC、LDL-C,升高 HDL-C,抑制 TNF-α、IL-6 水平,提高 NO、降低 ET-1 含量,差异有统计学意义(均 P<0.01).HE 染色显示丹蛭降糖胶囊高、中剂量组明显减轻主动脉内皮断裂、平滑肌排列紊乱及内膜 增 厚.Western blot 证实丹蛭降糖胶囊抑制 ASK1-JNK 通路关键蛋白(ASK1、p-ASK1、JNK、p-JNK、c-Jun)表达,差异有统计学意义(均 P<0.01).结论:丹蛭降糖胶囊通过抑制 ASK1-JNK 信号通路表达,改善大鼠糖脂代谢,减轻炎症反应及血管内皮损伤,延缓动脉粥样硬化进程.
Objective:To explore effect of Danzhi Jiangtang capsules on apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase(ASK1-JNK)signaling pathway in SD rats with diabetes mellitus(DM)combined with ather-osclerosis(AS).Methods:SD rats were used to establish DM combined with AS model with streptozotocin(STZ)so-lution and N-nitro-L-arginine methyl ester(L-NAME).The successfully modeled rats were randomly divided into the model group,atorvastatin group,and Danzhi Jiangtang capsules high-dose group 1.08 g/(kg·d),medium-dose group 0.54 g/(kg·d),and low-dose group 0.27 g/(kg·d),with a blank group also set up.Each drug administration group was given corresponding drug by gavage,while the model group and blank group were given 0.9%NaCl solu-tion of the same volume.After 8 weeks of intervention,the relevant indicators were detected.Results:Compared with the blank group,the model group had significantly increased fasting plasma glucose(FPG),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and endothelin-1(ET-1)(all P<0.01),and significantly decreased high-density lipoprotein cholesterol(HDL-C)and nitric oxide(NO)(all P<0.01).The relative expression of ASK1,p-ASK1,JNK,p-JNK,and c-Jun proteins in the aorta was significantly upregulated(all P<0.01).Compared with the model group,Danzhi Jiangtang capsules significantly reduced FPG,decreased TG,TC,and LDL-C,increased HDL-C,inhibited TNF-αand IL-6 lev-els,increased NO and decreased ET-1 content,with statistically significant differences(all P<0.01).HE staining showed that the high-and medium-dose groups of Danzhi Jiangtang capsules significantly alleviated aortic endothelial rupture,smooth muscle disorder,and intimal thickening.Western blot confirmed that Danzhi Jiangtang capsules in-hibited the expression of key proteins in the ASK1-JNK pathway(ASK1,p-ASK1,JNK,p-JNK,and c-Jun),with sta-tistically significant differences(all P<0.01).Conclusion:Danzhi Jiangtang capsules improve glucose and lipid me-tabolism,reduce inflammatory response,alleviate vascular endothelial injury,and delay the progression of atheroscle-rosis in rats by inhibiting the expression of the ASK1-JNK signaling pathway.
巫玉童;张栋飞;金磊;张智新;彭静静;徐甜;方朝晖
解放军联勤保障部队第九〇一医院,安徽 合肥 230031芜湖市中医院,安徽 芜湖 241000解放军联勤保障部队第九〇一医院,安徽 合肥 230031解放军联勤保障部队第九〇一医院,安徽 合肥 230031解放军联勤保障部队第九〇一医院,安徽 合肥 230031解放军联勤保障部队第九〇一医院,安徽 合肥 230031安徽中医药大学第一附属医院,安徽 合肥 230031
医药卫生
丹蛭降糖胶囊糖脂代谢c-Jun 氨基末端激酶凋亡信号调节激酶 1动脉粥样硬化糖尿病并发症
Danzhi Jiangtang capsuleGlucose and lipid metabolismc-jun N-terminal protein kinasesApop-tosis signal-regulating kinase 1AtherosclerosisDiabetic complications
《陕西中医》 2026 (5)
591-597,7
国家自然科学基金资助项目(82174153,81774286,81573944)安徽省卫生健康科研项目(AHWJ2023BAc20123)合肥综合性国家科学中心大健康研究院"揭榜挂帅"项目(2023CXMMTCM003)
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