首页|贝那普利灌胃对糖尿病肾病大鼠肾组织连接蛋白表达的影响

贝那普利灌胃对糖尿病肾病大鼠肾组织连接蛋白表达的影响

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目的 探讨贝那普利对于糖尿病肾病大鼠肾脏连接蛋白(Cxs)表达的影响。方法 将SD雄性大鼠分为对照组、糖尿病组、干预组,糖尿病组及干预组予以STZ 65 mg/kg一次性左下腹注射建立I型糖尿病模型,对照组予以相同剂量的枸橼酸盐缓冲液腹腔注射。造模成功后第2天开始,干预组予贝那普利10 mg/(kg·d)每日定时灌胃,对照组和糖尿病组给予等量0。9%氯化钠溶液灌胃,治疗8周,测量各组体质量,采用酶电解层析法检测空腹血糖,采用双抗体夹心法检测尿微量白蛋白;分别应用肌氨酸氧化酶法、酶偶联速率法检测血肌酐、血尿素。8周后处死大鼠,应用SABC法观察连接蛋白Cx37、Cx40、Cx43在肾脏病理组织的分布,免疫组化法检测连接蛋白Cx37、Cx40、Cx43表达,RT-qRCR法检测Cx37、Cx40、Cx43 mRNA表达。结果 与对照组相比,糖尿病组及干预组大鼠体质量较前明显下降,血糖较前明显升高(P均<0。05);干预组血尿素、血肌酐、尿微量白蛋白较糖尿病组均明显下降(P均<0。05)。糖尿病组Cx37、Cx43在出入球小动脉、近端肾小管分布明显减弱,干预组Cx37、Cx43在近端肾小管表达明显升高,糖尿病组可见Cx40在多处入球小动脉、致密斑分布明显减弱,干预组Cx40在致密斑分布增强。与糖尿病组比较,干预组Cx37、Cx40表达升高,差异有统计学意义(P均<0。05);干预组Cx43表达高于糖尿病组,差异无统计学意义(P>0。05)。Cx37 CT值在糖尿病组明显升高,且对照组Cx37 CT值高于干预组(P均<0。05)。三组Cx40 CT值差异无统计学意义,干预组Cx40 CT值较糖尿病组明显减小(P<0。05)。与对照组比较,糖尿病组Cx43 CT值明显下降,干预组Cx43 CT值明显上升,三组Cx43 CT值差异均有统计学意义(P均<0。05)。结论 贝那普利可上调糖尿病肾病大鼠肾脏连接蛋白表达,改善糖尿病肾病大鼠肾脏病理损伤,保护肾脏,延缓疾病进展。
Effect of intragastric administration of benazepril on expression of connectin in diabetic nephropathy rats
Objective To investigate the effect of benazepril on the expression of connexins(Cxs)in the renal tis-sues of diabetic nephropathy rats and its possible mechanism.Methods The SD male rats were divided into the control group,diabetes group,and intervention group.Rats in the diabetes group and intervention group were injected with STZ 65 mg/kg into the left lower abdomen once to establish the I-type diabetes models.Rats in the control group were injected with the same dose of citric acid buffer intraperitoneally.After the models were successfully established on the second day,rats in the intervention group were given benazepril 10 mg/(kg·d)by gavage daily at a fixed time,while rats in the control group and diabetes group were given the same volume of 0.9%sodium chloride solution.The treatment lasted for 8 weeks,during which,the body weight of each group was measured,fasting blood glucose was detected by enzymatic electrolytic chromatography,urinary microalbumin was detected by double-antibody sandwich method,and serum creatinine and urea were detected by sarcosine oxidase method and enzyme-coupled rate method,respectively.After 8 weeks,the rats were eu-thanized,and the distribution of connexin Cx37,Cx40,and Cx43 in the renal pathological tissues was observed by SABC method.The expression of connexin Cx37,Cx40,and Cx43 was detected by immunohistochemistry,and the expression of connexin Cx37,Cx40,and Cx43 mRNA was detected by RT-qRCR.Results Compared with the control group,the body weight of the diabetes group and the intervention group decreased significantly(P<0.05),and the blood glucose lev-el increased significantly(P<0.05);the blood urea nitrogen,blood creatinine,and urinary microalbuminuria of the inter-vention group were significantly lower than those of the diabetes group(all P<0.05).In the diabetes group,the distribu-tion of Cx37 and Cx43 in the efferent arterioles,afferent arterioles and proximal renal tubules was significantly weakened.In the intervention group,the expression of Cx37 and Cx43 in the proximal renal tubules significantly increased.In the dia-betes group,the distribution of Cx40 in multiple afferent arterioles and the macula densa was significantly weakened,and the distribution of Cx40 in the macula densa was enhanced in the intervention group.Compared with the diabetes group,the expression levels of Cx37 and Cx40 in the intervention group increased,with statistically significant differences(both P<0.05).The expression of Cx43 in the intervention group was higher than that of the diabetes group,but the difference was not statistically significant(P<0.05).The CT value of Cx37 in the diabetes group was significantly higher,and the Cx37 CT value in the intervention group was smaller than that of the control group(P<0.05).The CT value of Cx40 in the control group was not significantly different from those of the diabetes group and the intervention group,while the Cx40 CT value in the intervention group was significantly smaller than that of the diabetes group(all P<0.05).Compared with the control group,the Cx43 CT value in the diabetes group significantly decreased,and the Cx43 CT value in the intervention group significantly increased,and significant difference was found in the Cx43 CT value among all groups.Conclusion Benazepril can up-regulate the expression of renal connexin proteins in diabetic nephropathy rats,alleviate the pathological damage,protect the kidneys,and delay the progression of the disease.

diabetic nephropathyconnexinbenazeprilmicerats

史伟佳、任琳琳、曹延萍

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邯郸市第一医院肾内科,河北邯郸 056000

柘城县中医院医务科

糖尿病肾病 连接蛋白 贝那普利 大鼠

河北省卫生健康委员会医学科学研究课题计划项目邯郸市科学技术研究与发展计划项目

2022050321422083054

2024

山东医药
山东卫生报刊社

山东医药

CSTPCD
影响因子:1.225
ISSN:1002-266X
年,卷(期):2024.64(22)
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