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梓醇通过NLRP3/Caspase-1通路对糖尿病心肌病大鼠心脏的保护作用及机制

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目的 探讨梓醇通过NLRP3/Caspase-1通路对糖尿病心肌病大鼠心脏的保护作用及其机制.方法 从80只健康SD大鼠中随机选取70只,给予高脂高糖饲料,同时通过腹腔注射的方式,注射链脲佐菌素(streptozotocin,STZ)建立糖尿病大鼠模型,余下10只作为对照组正常饲料喂养.将造模成功的60只大鼠(10只大鼠未达模型标准被淘汰)随机分成模型组、梓醇低剂量组、中剂量组、高剂量组,每组各15只,按照100、300、900 mg/kg的量每日灌胃1次,连续干预8 w,期间保持高脂高糖喂养;对照组和模型组灌胃生理盐水.最后一次灌胃结束后,超声检测大鼠心功能,HE染色观察大鼠心肌形态学变化,蛋白免疫印迹法(Western Blot)检测大鼠心肌组织NLRP3、Caspase-1蛋白表达量,大鼠血清中白细胞介素-18(IL-18)、白细胞介素-1β(IL-1β)含量经酶联免疫吸附法(ELISA)检测.结果 与对照组相比,模型组大鼠左心室缩短率(fractional shortening,FS)、左心室射血分数(left ventricular ejection fraction,LVEF)均显著降低(P<0.05),HE染色结果可见心肌纤维肿胀、排列紊乱、纤维束间隔增宽,大鼠心肌组织NLRP3蛋白、Caspase-1蛋白表达量和血清中IL-1β、IL-18水平均显著增高(P<0.05).梓醇低、中、高剂量组LVEF、FS与模型组比较均明显改善(P<0.05),大鼠心肌组织病理学损伤明显改善,同时心肌组织NLRP3、Caspase-1蛋白表达及血清IL-1β、IL-18含量均明显降低(P<0.05),仅梓醇低剂量组Caspase-1蛋白表达无差异.结论 梓醇保护DCM大鼠心肌组织可能是通过调控NL-RP3/Caspase-1信号通路,抑制DCM大鼠心肌细胞焦亡.
Protective Effect and Mechanism of Catalpol on Rats with Diabetic Cardiomyopathy Through NLRP3/Caspase-1 Pathway
Objective To investigate the protective effect of catalpol on the heart of diabetic cardiomyopathy rats through NL-RP3/Caspase-1 pathway and its mechanism.Methods 70 heacthy SD rats randomly selected from 80 healthy SD rats were fed high-fat and high-sugar diet,and were injected peritoneally with streptozotocin to establish diabetic rat model,and the remaining 10 were fed normal diet as control group.A total of 60 successful rats were randomly divided into model group,catalpol low-dose group,catalpol medium-dose group and catalpol high-dose group(15 rats in each group).The low,medium and high dose groups of catal-pol were given 100 mg/kg,300 mg/kg and 900 mg/kg intragastatically once a day for 8 weeks,during which high fat and high sugar feeding was maintained;the control group and model group were given normal diet and normal saline.After the last gavage,the cardi-ac function of rats was detected by ultrasound,the myocardial morphological changes were observed by HE staining,and the protein expressions of NLRP3 and Caspase-1 in myocardial tissue were detected by Western Blot.The contents of interleukin-1 β(IL-1 β)and interleukin-18(IL-18)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA).Results The left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(FS)in the model group exhibited a significant de-crease compared to the control group(P<0.05).HE staining showed swelling,disordered arrangement of myocardial fibers and wide-ning of fiber bundle interval.In myocardial tissue,the expression of Caspase-1 and NLRP3 proteins were significantly upregulated,accompanied by a marked increase in the concentrations of IL-1β and IL-18 in serum(P<0.05).Compared with the model group,LVEF and FS in low,medium and high dose groups of catalpa were significantly improved(P<0.05),the pathological injury of myo-cardium was significantly improved,and the protein expressions of NLRP3 and Caspase-1 in myocardium and the contents of IL-1 βand IL-18 in serum were significantly decreased(P<0.05).In high dose group of catalpol,the improvement was more significant.Conclusion Catalpol protects myocardium in DCM rats by regulating NLRP3/Caspase-1 signaling pathway and inhibiting scorch death of myocardium in DCM rats.

catalpoldiabetic cardiomyopathypyroptosisNLRP3/Caspase-1 signaling pathway

于平、展美屏、祝欣欣、徐伟、栾佳潓、谭迪

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锦州医科大学,辽宁锦州 121000

梓醇 糖尿病心肌病 细胞焦亡 NLRP3/Caspase-1信号通路

辽宁省大学生创新训练项目

S202310160028

2024

锦州医科大学学报
辽宁医学院

锦州医科大学学报

影响因子:0.802
ISSN:1674-0424
年,卷(期):2024.45(3)