Yu Hongmei, Wang Mei, Yu Jingshi, Tang Haitao, Xu Qing, Cheng Ning, Luo Xiaoxiao, Wang Yurong, Ge Haitao, Qiang Lei, Tang Wei, Gu Harvest F
Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Suzhong Pharmaceutical Research Institute, Nanjing, China.
Front Pharmacol. 2023 Aug 1;14:1215996. doi: 10.3389/fphar.2023.1215996. eCollection 2023.
As a traditional Chinese medicine (L.) in the form of Huangkui (HK) capsule has been used as a medication for kidney diseases, including diabetic nephropathy (DN), in China. The most significant effect of HK capsule treatment in kidney diseases is the reduction of albuminuria and proteinuria. To evaluate the efficacy of HK capsule in the regression of DN, in the current study, we analyzed the biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys of db/db mice, the animal model for type 2 diabetes and DN. Huangkui capsules (0.84 g/kg/d) or vehicle were administered daily via oral gavage for 4 weeks in db/db mice. Urinary albumin-to-creatinine ratio and blood glucose levels were measured during the whole experimental period. Five biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys were selected, namely, col4a3, slc5a2, slc34a1, slc12a3, and slc4a1, and their activities at mRNA and protein levels before and after HK capsule treatment were analyzed by real-time RT-PCR and immunohistochemistry. After HK capsule treatment for 4 weeks, the urinary albumin-to-creatinine ratio in db/db mice was found to be significantly decreased. The activities of col4a3, slc5a2, slc34a1, slc12a3, and slc4a1 in the kidneys were upregulated in db/db mice prior to the treatment but downregulated after HK capsule treatment. Further analyses of the fields of whole kidney tissue sections demonstrated that the number of nephrons in the kidneys of db/db mice with HK capsule treatment was higher than that in the kidneys of db/db mice without HK capsule treatment. Thereby, the current study provides experimental evidence confirming the medical efficacy of in the reduction of albuminuria and proteinuria, suggesting that may have pharmacological efficacy in the regression of the development of type 2 diabetes-DN.
在中国，黄葵（HK）胶囊形式的一种传统中药已被用作治疗肾脏疾病（包括糖尿病肾病（DN））的药物。HK胶囊治疗肾脏疾病的最显著效果是降低蛋白尿和白蛋白尿。为了评估HK胶囊在DN消退中的疗效，在本研究中，我们分析了2型糖尿病和DN动物模型db/db小鼠肾脏中肾小球、近端和远端曲管中的生物标志物。在db/db小鼠中，通过口服灌胃每日给予黄葵胶囊（0.84 g/kg/d）或赋形剂，持续4周。在整个实验期间测量尿白蛋白与肌酐比值和血糖水平。选择了肾脏中肾小球、近端和远端曲管中的五种生物标志物，即col4a3、slc5a2、slc34a1、slc12a3和slc4a1，并通过实时RT-PCR和免疫组织化学分析了HK胶囊治疗前后它们在mRNA和蛋白质水平的活性。HK胶囊治疗4周后，发现db/db小鼠的尿白蛋白与肌酐比值显著降低。db/db小鼠肾脏中col4a3、slc5a2、slc34a1、slc12a3和slc4a1的活性在治疗前上调，但在HK胶囊治疗后下调。对整个肾脏组织切片区域的进一步分析表明，接受HK胶囊治疗的db/db小鼠肾脏中的肾单位数量高于未接受HK胶囊治疗的db/db小鼠肾脏中的肾单位数量。因此，本研究提供了实验证据，证实了其在降低白蛋白尿和蛋白尿方面的医学疗效，表明其可能在2型糖尿病-DN发展的消退中具有药理作用。
