Ren Gaofei, Jiao Pengfei, Yan Yushan, Ma Xiaojun, Qin Guijun
Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Diabetes Metab Syndr Obes. 2023 Apr 26;16:1193-1205. doi: 10.2147/DMSO.S407177. eCollection 2023.
Inflammation and oxidative stress contribute to the development of diabetic nephropathy (DN). Baicalin (BA) shows renal protection against DN through its anti-inflammatory and anti-oxidant properties. However, the molecular mechanism by which BA exerts the therapeutic effects on DN remains to be investigated.
The db/db mice and high glucose (HG)-induced HK-2 cells were used as the in vivo and in vitro model of DN, respectively. The effects of BA were assessed by detecting the related blood and urine biochemical parameters, kidney histopathology, inflammatory cytokine production, oxidative stress indicators, and apoptosis. Cell viability and apoptosis were detected by CCK-8 assay and TUNEL assay, respectively. Related protein levels were measured by an immunoblotting method.
In db/db model mice, BA reduced serum glucose concentration, decreased blood lipid levels, ameliorated kidney functions, and decreased histopathological changes in kidney tissues. BA also alleviated oxidative stress and inflammation in db/db mice. In addition, BA blocked the activation of sphingosine kinases type 1/sphingosine 1-phosphate (SphK1/S1P)/NF-κB pathway in db/db mice. In HK-2 cells, BA hindered HG-induced apoptosis, oxidative stress and inflammation, while overexpression of SphK1 or S1P could reverse these effects. BA alleviated HG-induced apoptosis, oxidative stress and inflammation in HK-2 cells through the S1P/NF-κB pathway. Furthermore, BA blocked the NF-κB signaling by diminishing p65 nuclear translocation via the SphK1/S1P pathway.
Our study strongly suggests that BA protects against DN via ameliorating inflammation, oxidative stress and apoptosis through the SphK1/S1P/NF-κB pathway. This study provides a novel insight into the therapeutic effects of BA in DN.
炎症和氧化应激促成糖尿病肾病（DN）的发展。黄芩苷（BA）通过其抗炎和抗氧化特性对DN具有肾脏保护作用。然而，BA对DN发挥治疗作用的分子机制仍有待研究。
分别将db/db小鼠和高糖（HG）诱导的HK-2细胞用作DN的体内和体外模型。通过检测相关血液和尿液生化参数、肾脏组织病理学、炎性细胞因子产生、氧化应激指标和细胞凋亡来评估BA的作用。分别通过CCK-8法和TUNEL法检测细胞活力和细胞凋亡。采用免疫印迹法测定相关蛋白水平。
在db/db模型小鼠中，BA降低血清葡萄糖浓度，降低血脂水平，改善肾功能，并减少肾组织的组织病理学变化。BA还减轻了db/db小鼠的氧化应激和炎症。此外，BA阻断了db/db小鼠中1型鞘氨醇激酶/鞘氨醇-1-磷酸（SphK1/S1P）/NF-κB信号通路的激活。在HK-2细胞中，BA抑制HG诱导的细胞凋亡、氧化应激和炎症，而SphK1或S1P的过表达可逆转这些作用。BA通过S1P/NF-κB信号通路减轻HG诱导的HK-2细胞凋亡、氧化应激和炎症。此外，BA通过SphK1/S1P信号通路减少p65核转位，从而阻断NF-κB信号传导。
我们的研究强烈表明，BA通过SphK1/S1P/NF-κB信号通路改善炎症、氧化应激和细胞凋亡，从而对DN起到保护作用。本研究为BA在DN中的治疗作用提供了新的见解。
