School of Pharmacy, North China University of Science and Technology, Tangshan 063210, Hebei, PR China.
Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, Hebei, PR China.
Aging (Albany NY). 2022 Apr 19;14(8):3416-3424. doi: 10.18632/aging.204019.
D-Chiro-inositol (DCI) exerts a hypoglycaemic effect, participates in lipid metabolism and reduces kidney damage. In this study, we preliminarily explored the protective effect of DCI on renal injury in diabetic mice. Male db/db mice were used in this study. After treatment with DCI (35 and 70 mg/kg/d) for 6 consecutive weeks, random blood glucose (RBG) measurements were conducted at 0 and 6 weeks. Creatinine (Cr) and serum blood urea nitrogen (BUN) levels were measured using assay kit, and morphological changes in the kidneys were observed by HE staining, Masson staining and electron microscopy. Immunohistochemical and Western blot experiments were used to examine the protein expression of matrix metalloproteinase-9 (MMP-9), nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ). We discovered that the increased RBG levels were alleviated after treatment with DCI. Moreover, the Cr and BUN levels were reduced, glomerular mesangial hyperplasia was alleviated, and the degree of renal fibrosis was reduced. In addition, DCI improved the protein expression of MMP-9 and PPAR-γ in kidney tissue, which in turn inhibited NF-κB protein expression, as shown by immunohistochemistry and Western blotting. Our findings showed that DCI ameliorated the renal injury induced by diabetes by upregulating MMP-9 and PPAR-γ expression and downregulating NF-κB expression. We preliminarily concluded that the renal protective effect of DCI on diabetic mice may occurs through the MMP-9/NF-κB signalling pathway.
D-手性肌醇（DCI）具有降血糖作用，参与脂质代谢，并减轻肾脏损伤。在这项研究中，我们初步探讨了 DCI 对糖尿病小鼠肾脏损伤的保护作用。本研究采用雄性 db/db 小鼠。连续 6 周给予 DCI（35 和 70mg/kg/d）治疗后，在 0 和 6 周时进行随机血糖（RBG）测量。使用试剂盒测量肌酐（Cr）和血清血尿素氮（BUN）水平，并通过 HE 染色、Masson 染色和电子显微镜观察肾脏的形态变化。免疫组化和 Western blot 实验用于检测基质金属蛋白酶-9（MMP-9）、核因子-κB（NF-κB）和过氧化物酶体增殖物激活受体-γ（PPAR-γ）的蛋白表达。我们发现，用 DCI 治疗后，升高的 RBG 水平得到缓解。此外，Cr 和 BUN 水平降低，肾小球系膜增生减轻，肾纤维化程度降低。此外，DCI 改善了肾脏组织中 MMP-9 和 PPAR-γ 的蛋白表达，从而通过免疫组化和 Western blot 抑制了 NF-κB 蛋白表达。我们的研究结果表明，DCI 通过上调 MMP-9 和 PPAR-γ 的表达和下调 NF-κB 的表达来改善糖尿病引起的肾脏损伤。我们初步得出结论，DCI 对糖尿病小鼠的肾脏保护作用可能通过 MMP-9/NF-κB 信号通路发生。
