Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis
Vitamin D3 alleviates lung fibrosis of type 2 diabetic rats via SIRT3 mediated suppression of pyroptosis
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DOI：
10.1007/s10495-023-01878-6
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发表时间：
2023-08
期刊：
影响因子：
7.2
通讯作者：
Lulu Tang;D. Zhang;Yujing Zhang;Yangyang Peng;Mengxin Li;Hanlu Song;Hao Chen;Wenjie Li;Xing Li
中科院分区：
文献类型：
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作者：
Lulu Tang;D. Zhang;Yujing Zhang;Yangyang Peng;Mengxin Li;Hanlu Song;Hao Chen;Wenjie Li;Xing Li
方法SD大鼠随机分为正常对照组（NC）、糖尿病模型对照组（MC）、低剂量维生素D3组（LVD）、中剂量维生素D3组（MVD）、高剂量维生素D3组（HVD）和二甲双胍阳性对照组（PC）。采用高糖高脂饮食联合链脲佐菌素（STZ）诱导2型糖尿病模型，并分别给予维生素D3或二甲双胍干预10周。检测各组大鼠血糖、体重、摄食量、饮水量、尿量、肺组织形态学、肺组织羟脯氨酸水平、免疫组化、TUNEL染色、炎性细胞因子分泌及相关蛋白表达。形态学参数显示糖尿病大鼠肺纤维化严重。有趣的是，VD3干预至少部分逆转了糖尿病诱导的改变。在糖尿病肺中，脓毒症相关蛋白的表达上调，而VD3逆转了这种变化。结论糖尿病大鼠肺组织存在纤维化改变，VD3可能通过抑制SIRT3介导的肺组织细胞凋亡而有效地改善糖尿病肺纤维化。
PurposeWe aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis.MethodsSprague-Dawley rats were assigned to normal control (NC), diabetic model control (MC), low-dose VD3 (LVD), medium-dose VD3 (MVD), high-dose VD3 (HVD) and metformin positive control (PC) groups. Type 2 diabetes model was induced by a high-sugar, high-fat diet combined with STZ injection, and subsequently intervened with VD3 or metformin for 10 weeks. Blood glucose, body weight, food intake, water intake, urine volume, morphology, lung hydroxyproline level, immunohistochemistry, TUNEL staining, inflammatory cytokines secretion and related protein expression were analyzed.ResultsDiabetic rats exhibited significant impairments in fasting blood glucose, insulin resistance, body weight, food intake, water intake, and urine volume. While morphological parameters, diabetic rats exhibited severe lung fibrosis. Intriguingly, VD3 intervention reversed, at least in part, the diabetes-induced alterations. The expression of pyroptosis-related proteins was up-regulated in diabetic lungs whereas the changes were reversed by VD3. In the meanwhile, SIRT3 expression was down-regulated in diabetic lungs while VD3 up-regulated it.ConclusionFibrotic changes were observed in diabetic rat lung tissue and our study indicates that VD3 may effectively ameliorate diabetic pulmonary fibrosis via SIRT3-mediated suppression of pyroptosis.