摘要
目的基于p38丝裂原活化蛋白激酶/核因子-κB(p38 MAPK/NF-κB)信号通路探讨藏红花素对糖尿病心肌病(DCM)大鼠的影响。方法取45只Wistar大鼠,随机选择8只作为正常组,其余大鼠采用高糖高脂饮食12周并负荷一次性30 mg/kg链脲佐菌素的方法构建DCM模型。将32只造模成功的大鼠随机分为模型组、藏红花素组、藏红花素+p38 MAPK抑制剂组和藏红花素+p38 MAPK激动剂组,每组8只。藏红花素组给予50 mg/kg藏红花素腹腔注射,藏红花素+p38 MAPK抑制剂组给予50 mg/kg藏红花素和5 mg/kg SB203580腹腔注射,藏红花素+p38 MAPK激动剂组给予50 mg/kg藏红花素和2 mg/kg ANS腹腔注射,正常组和模型组给予等体积生理盐水腹腔注射,均1次/d。连续注射12周后,心脏超声检测大鼠心功能指标[左心室收缩末期压(LVESD)、左心室舒张末期压(LVEDD)、左心室短轴缩短率(LVFS)],ELISA法检测血清心肌酶[谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)]和炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)]水平,苏木精-伊红、马森染色观察心肌组织病变和纤维化情况,RT-PCR法、免疫组织化学法检测心肌组织中p38 MAPK、NF-κB p65、转化生长因子-β1(TGF-β1)、I型胶原蛋白(Col-I)mRNA和蛋白表达情况。结果与模型组比较,藏红花素组、藏红花素+p38 MAPK抑制剂组大鼠LVESD、LVEDD及血清AST、LDH、CK-MB、IL-1β、IL-18、TNF-α水平均明显降低(P均<0.05),LVFS明显升高(P<0.05);心肌组织病变和纤维化情况均明显改善,心肌组织损伤评分和胶原容积分数均明显降低(P均<0.05);心肌组织中p38 MAPK、NF-κB p65、TGF-β1、Col-I mRNA相对表达量和蛋白表达积分吸光度均明显降低(P均<0.05)。与藏红花素组比较,SB203580可显著增强藏红花素对DCM大鼠心功能指标、心肌酶和炎症因子水平、心肌组织病变和纤维化情况、p38 MAPK/NF-κB信号通路相关因�
Objective It is to investigate the effect of Crocin on diabetic cardiomyopathy(DCM)in rats via p38 mitogen-activated protein kinase/nuclear factor-κB(p38 MAPK/NF-κB)signaling pathway.Methods Forty-five Wistar rats were taken,in which 8 rats were randomly selected as normal group,and the remaining rats were fed with high-sugar and high-fat diet for 12 weeks and loaded with 30 mg/kg streptozotocin to establish models of DCM.32 successfully modeled rats were randomly divided into model group,Crocin group,Crocin+p38 MAPK inhibitor group and Crocin+p38 MAPK agonist group,with 8 rats in each group.The Crocin group was given 50 mg/kg Crocin intraperitoneally,the Crocin+p38 MAPK inhibitor group was given 50 mg/kg Crocin and 5 mg/kg SB203580 intraperitoneally,the Crocin+p38 MAPK agonist group was given 50 mg/kg Crocin and 2 mg/kg ANS intraperitoneally,and the normal group and model group were given equal volumes of normal saline by intraperitoneal injection,all once daily.After 12 weeks of administration,the cardiac function indexes[left ventricular end-systolic diameter index(LVESD),left ventricular end diastolic diameter(LVEDD),left ventricular fractional shortening(LVFS)]of the rats were detected by cardiac ultrasound,the serum levels of myocardial enzyme[aspartate transaminase(AST),lactate dehydrogenase(LDH),creatine kinase isoenzyme MB(CK-MB)]and inflammatory factors[interleukin-1β(IL-1β),IL-18,tumor necrosis factor-α(TNF-α)]in myocardial tissue were detected by ELISA,the myocardial tissue pathological changes and fibrosis were observed by hematoxylin-eosin or masson staining,The mRNA and protein expressions of p38 MAPK,NF-κB p65,transforming growth faction-β1(TGF-β1),type I collagen(Col-I)were detected by RT-PCR or immunohistochemical(IHC)method.Results Compared with the model group,the LVESD,LVEDD,and serum levels of AST,LDH,CK-MB,IL-1β,IL-18,TNF-αin the Crocin group and Crocin+p38 MAPK inhibitor group were significantly decreased,and the LVFS was significantly increased(all P<0.05);the myocardial tissue
作者
王立哲
王振贤
马晓伟
WANG Lizhe;WANG Zhenxian;MA Xiaowei(Handan Central Hospital,Handan 056008,Hebei,China)
出处
《现代中西医结合杂志》
CAS
2024年第13期1757-1764,共8页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
河北省医学科学研究课题计划项目(20211627)
邯郸市科学技术研究与发展计划项目(1823208041ZC)。
