摘要
目的:探讨黄芩苷调节GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对糖尿病心肌病(DCM)大鼠炎症反应的影响。方法:取SD大鼠通过高脂饲料喂养+腹腔注射链脲佐菌素(STZ)来构建DCM模型,并随机分为模型组、黄芩苷(120 mg/kg)组、pc-NC(空载质粒)组、黄芩苷+pccGAS(120 mg/kg+cGAS过表达质粒)组,每组各12只;另取12只正常大鼠以正常饲料喂养并于腹腔内注射等剂量柠檬酸缓冲液,设为对照组,采用黄芩苷和质粒分组干预后测量各组大鼠空腹血糖(FBG),超声检测大鼠心功能,并比较各组左心室射血分数(EF)和等容舒张时间(IVRT);TUNEL染色检测大鼠心肌细胞凋亡;ELISA法检测各组大鼠血清肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)与心肌肌钙蛋白I(cTnI)水平、血清及心肌组织炎症指标C-反应蛋白(CRP)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)水平;免疫印迹法检测各组大鼠心肌组织cGAS-STING通路蛋白表达。结果:与对照组比较,模型组大鼠FBG、心肌细胞凋亡率、血清CK-MB、LDH、cTnI、CRP、IL-18与TNF-α水平、心肌组织CRP、IL-18与TNF-α水平、cGAS与STING蛋白表达均升高(P<0.05),IVRT、EF均降低(P<0.05)。与模型组比较,黄芩苷组大鼠FBG、心肌细胞凋亡率、血清CK-MB、LDH、cTnI、CRP、IL-18与TNF-α水平、心肌组织CRP、IL-18与TNF-α水平、cGAS与STING蛋白表达均降低(P<0.05),IVRT、EF均升高(P<0.05);pc-NC组大鼠各指标无明显变化(P>0.05)。与黄芩苷组比较,黄芩苷+pc-cGAS组大鼠FBG、心肌细胞凋亡率、血清CK-MB、LDH、cTnI、CRP、IL-18与TNF-α水平、心肌组织CRP、IL-18与TNF-α水平、cGAS与STING蛋白表达均升高(P<0.05),IVRT、EF均降低(P<0.05)。结论:黄芩苷可通过阻止cGAS-STING信号激活而降低血糖水平,抑制DCM大鼠炎症,进而减轻大鼠心肌细胞凋亡及心功能损伤。
Objective:To investigate the effects of Baicalin on inflammatory responses in cardiomyopathy(DCM)rats by regulating the cGAS-STING signaling pathway.Methods:A total of 48 SD rats were fed a high-fat diet and injected intraperitoneally with streptozotocin(STZ)to establish a DCM model.The rats were randomly divided into four groups:the model group,the Baicalin(120 mg/kg)group,the pc-NC(empty plasmid)group,and the Baicalin and pc-cGAS(120 mg/kg+cGAS overexpression plasmid)group,with 12 rats in each group.Additionally,12 normal rats were fed a normal diet and injected intraperitoneally with an equal dose of citrate buffer solution,serving as the control group.After intervention with Baicalin and plasmids,fasting blood glucose(FBG)levels were measured,heart function was assessed by ultrasound,and left ventricular ejection fraction(EF)and isovolumic relaxation time(IVRT)were compared among the groups;TUNEL staining was used to detect myocardial cell apoptosis;ELISA was employed to measure the levels of creatine kinase-MB(CK-MB),lactate dehydrogenase(LDH),and cardiac troponin I(cTnI)in serum,as well as serum and myocardial tissue levels of inflammatory markers like C-reactive protein(CRP),interleukin-18(IL-18),and tumor necrosis factor-α(TNF-α);Western blotting was used to detect the expressions of cGAS-STING pathway proteins in myocardial tissue.Results:Compared with those in the control group,the FBG,the myocardial cell apoptosis rate,the levels of CK-MB,LDH,cTnI,CRP,IL-18,and TNF-αin serum,the levels of CRP,IL-18,and TNF-αin myocardial tissue,and the cGAS and STING protein expressions in the model group were significantly increased(P<0.05),and IVRT and EF were significantly decreased(P<0.05).Compared with those in the model group,the FBG,the myocardial cell apoptosis rate,the levels of CK-MB,LDH,cTnI,CRP,IL-18,and TNF-αin serum,the levels of CRP,IL-18,and TNF-αin myocardial tissue,and the cGAS and STING protein expressions in the Baicalin group were decreased(P<0.05),and IVRT and EF were increased(P<0.05);the pc-NC group showed no significant change in these indicators(P>0.05).Compared with those in the Baicalin group,the FBG,the myocardial cell apoptosis rate,the levels of CK-MB,LDH,cTnI,CRP,IL-18,and TNF-αin serum,the levels of CRP,IL-18,and TNF-αin myocardial tissue,and the cGAS and STING protein expressions in the Baicalin and pc-cGAS group were increased(P<0.05),and IVRT and EF were decreased(P<0.05).Conclusion:Baicalin can reduce blood glucose levels,inhibit inflammation in DCM rats,and alleviate myocardial cell apoptosis and heart function damage by preventing the activation of the cGAS-STING signaling pathway.
作者
宣疆英
王燕平
张义林
XUAN Jiangying;WANG Yanping;ZHANG Yilin(Pharmacy Department,Hangzhou Ninth People's Hospital,Hangzhou Zhejiang 310000,China;Cardiovascular Department of Internal Medicine,Hangzhou Ninth People's Hospital,Hangzhou Zhejiang 310000,China)
出处
《新中医》
2025年第4期165-171,共7页
New Chinese Medicine
基金
浙江省卫生健康科技计划项目(2022RC072)。
