Liu Feiyan, Zhu Yan, He Jie, Chen Huimin, Cao Caixia, Xiong Di, Zhou Ying, Hu Ling
Department of Nephrology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
Department of Endocrinology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
Exp Ther Med. 2022 Nov 8;24(6):747. doi: 10.3892/etm.2022.11683. eCollection 2022 Dec.
The present study aimed to compare the therapeutic effect of sodium/glucose cotransporter 2 (SGLT2) inhibitor and benazepril on diabetic nephropathy (DN) rats and provide a potential novel agent for the clinical treatment of DN. The DN model was established on rats. Animals were dosed orally with SGLT2 and benazepril daily for 4 weeks. The pathological state of renal tissues were evaluated using hematoxylin and eosin, Masson and periodic acid-Schiff staining. The change in the morphology of renal tissues was observed through transmission electron microscopy. Western blotting was utilized to determine the expression level of TGF-β, N-terminal fragment of the B-type natriuretic peptide precursor (NT-proBNP) and matrix metalloproteinase-9 (MMP-9). The expression level of endothelin 1 (ET-1), von Willebrand factor (vWF), collagen (col)-I and α smooth muscle actin (α-SMA) in renal tissues was visualized using immunohistochemical assay. Significant pathological changes in the glomerular basement membrane, mesangial membrane, renal tubules, lumen, renal interstitial region and renal tubular epithelial cells were observed in DN rats, accompanied by increased collagen fibers. SGLT2 inhibitor treatment demonstrated more alleviatory effects on the pathological changes of renal tissues compared with benazepril. Compared with control, TGF-β and NT-proBNP were upregulated in DN rats, accompanied by the downregulation of MMP-9, ET-1, vWF, col-I and α-SMA, which were markedly reversed by treatment with SGLT2 inhibitor and benazepril. Compared with benazepril, the effects of SGLT2 inhibitor on the expression level of TGF-β, NT-proBNP, MMP-9, ET-1, vWF, col-I and α-SMA were more significant. Overall, SGLT2 inhibitor demonstrated an increased therapeutic effect against DN rats compared with benazepril by regulating cytokines, renal fibrosis and extracellular matrix degradation.
本研究旨在比较钠/葡萄糖协同转运蛋白2（SGLT2）抑制剂与贝那普利对糖尿病肾病（DN）大鼠的治疗效果，并为DN的临床治疗提供一种潜在的新型药物。在大鼠身上建立DN模型。动物每天口服SGLT2抑制剂和贝那普利，持续4周。使用苏木精和伊红、Masson和高碘酸-希夫染色评估肾组织的病理状态。通过透射电子显微镜观察肾组织形态的变化。利用蛋白质免疫印迹法测定转化生长因子-β（TGF-β）、B型利钠肽前体N端片段（NT-proBNP）和基质金属蛋白酶-9（MMP-9）的表达水平。采用免疫组织化学法观察肾组织中内皮素1（ET-1）、血管性血友病因子（vWF）、胶原蛋白（col）-I和α平滑肌肌动蛋白（α-SMA）的表达水平。DN大鼠的肾小球基底膜、系膜膜、肾小管、管腔、肾间质区域和肾小管上皮细胞出现明显的病理变化，伴有胶原纤维增加。与贝那普利相比，SGLT2抑制剂治疗对肾组织的病理变化具有更明显的缓解作用。与对照组相比，DN大鼠中TGF-β和NT-proBNP上调，同时MMP-9、ET-1、vWF、col-I和α-SMA下调，而SGLT2抑制剂和贝那普利治疗可明显逆转这种变化。与贝那普利相比，SGLT2抑制剂对TGF-β、NT-proBNP、MMP-9、ET-1、vWF、col-I和α-SMA表达水平的影响更显著。总体而言，与贝那普利相比，SGLT2抑制剂通过调节细胞因子、肾纤维化和细胞外基质降解，对DN大鼠显示出更强的治疗效果。
