摘要
目的:通过观察db/db糖尿病肾病(DN)小鼠的心肌肥大和心肌损伤,进而探讨肾元颗粒改善DN小鼠心肌肥大和凋亡的可能作用机制。方法:db/db小鼠45只随机分为模型组、厄贝沙坦组和肾元颗粒组,15只同背景野生型(WT)小鼠为空白组。ELISA检测血清成纤维细胞生长因子23(FGF23)和尿微量白蛋白含量;全自动生化仪检测肾功能;小鼠肾脏和心脏病理采用HE和Masson染色;Real-time PCR肾脏Kl和心脏ANP、Bax、Bcl-2 mRNA;Western blot检测肾脏Kl和心脏Bax、Bcl-2蛋白;免疫组化检测心脏ANP、p-CaMKⅡ蛋白含量。结果:与空白组比较,模型组小鼠肾单位出现受损,小球系膜基质增多,基底膜增厚,肾小管上皮细胞肥大,心脏心肌细胞排列紊乱,体积增大,伴有明显的胶原纤维沉积,血清FGF23、BUN、Scr和24h尿微量白蛋白含量增加(P<0.01),肾脏Kl mRNA和蛋白显著减少(P<0.01),心脏ANP mRNA、Bax mRNA和蛋白表达增加(P<0.01),Bcl-2 mRNA和蛋白表达量减少(P<0.01),心脏p-CaMKⅡ蛋白含量增加;灌胃12周后,肾元颗粒组和厄贝沙坦组肾脏和心脏病理表现均显著减轻,血清FGF23含量减少(P<0.05,P<0.01),肾脏Kl和心脏Bcl-2mRNA和蛋白含量增加(P<0.01),心脏ANP mRNA和Bax mRNA及蛋白含量减少(P<0.01),心脏p-CaMKⅡ蛋白表达减少。结论:肾元颗粒可通过上调肾脏Kl蛋白表达,降低CaMKⅡ活性,抑制FGF23/CaMKⅡ信号通路来抑制肥大细胞表达,降低凋亡的发生,达到心肌细胞的保护作用。
Objective: By observing myocardial hypertrophy and myocardial injury in db/db mice with diabetic nephropathy(DN) to explore the possible protection mechanisms of Shenyuan Granules on myocardial hypertrophy and apoptosis in db/db mice with DN. Methods: Forty-five db/db mice were randomly divided into the model group, irbesartan group, and Shenyuan Granules group, and 15 WT mice of the same background were used as blank control group. Serum FGF23 and urine microalbumin content were measured by ELISA;Renal function was detected by a fully automatic biochemical analyzer;HE and Masson staining were used in mouse kidney and heart pathology;Real-time PCR was used to detect the mRNA expressions of kidney blank control and cardiac ANP, Bax, Bcl-2;Western blot was used to detect the protein expressions of kidney Kl and cardiac Bax and Bcl-2;the cardiac ANP and p-CaMKⅡ protein contents were detected by immunohistochemistry(IHC). Results: Compared with the blank control group, the nephrons of the model group were damaged, the glomerular mesangial matrix was increased, the basement membrane was thickened, the renal tubular epithelial cells were enlarged, the cardiac myocytes were disorderly arranged, and the volume was increased, with obvious collagen fibers deposition. Serum FGF23, BUN, Scr and 24 h urine microalbumin content increased(P<0.01), mRNA and protein expressions of kidney Kl decreased significantly(P<0.01), m RNA and protein expressions of cardiac ANP and Bax increased(P<0.01), mRNA and protein expressions of Bcl-2 decreased(P<0.01), the protein content of cardiac p-CaMK Ⅱ increased. After 12 weeks of gavage, the renal and cardiac pathological manifestations of the Shenyuan Granules group and the irbesartan group were significantly reduced, the serum FGF23 contents were reduced(P<0.05, P<0.01), mRNA and protein expressions of kidney Kl and cardiac Bcl-2 increased(P<0.01), mRNA and protein expressions of cardiac Bax and ANP reduced(P<0.01), and protein expressions of cardiac p-CaMKⅡ decreased. Conclusion: She
作者
朱国双
王岚
金善善
孙龙
邓丹芳
林腊梅
王小琴
ZHU Guo-shuang;WANG Lan;JIN Shan-shan;SUN Long;DENG Dan-fang;LIN La-mei;WANG Xiao-qin(Hubei University of Chinese Medicine,Wuhan 430061,China;Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430061,China;Hubei Academy of Traditional Chinese Medicine,Wuhan 430061,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2020年第5期2401-2406,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81874439,No.81703991)。
