1.The effects of calcium dobesilate combined with irbesartan in treating early diabetic nephropathy
Mei PENG ; Xiancong WANG ; Kai LUO ; Qinghua ZHENG ; Huanlan WANG
Chinese Journal of Primary Medicine and Pharmacy 2012;19(16):2434-2435
ObjectiveTo observe the therapeutic effects of calcium dobesilate combined with irbesartan in treating early diabetic nephropathy ( DN ).Methods65 patients with early DN were randomly divided into two groups,experiment group( irbesartan plus calcium dobesilate,n =34) and control group( irbesartan,n =31 ).After 24 week treatment,the urinary albumin excretion rate(UAER),fasting blood glucose ( FBG ),postprandial blood glucose (PBG) and glycosylated hemoglobin(HbA1c) were detected and compared between two groups before and after treat ment.ResultsUAER after treatment was significantly reduced in both 2 groups(t =8.074,12.89,all P<0.01),and the decrement in the experiment group was more obvious than that in the control group with statistical significance ( t =3.965,P < 0.05).ConclusionCalcium dobesilate combined with irbesartan has good effects in the treatment of early DN.
2.Salvianolic Acid F Regulates Bax/Caspase-3/GSDME Signaling Pathway to Inhibit Pyroptosis of HK-2 Cells
Xiancong SHI ; Zhishen XIE ; Liang ZHAO ; Jiajun WANG ; Yafei DUAN ; Pan WANG ; Zhenqiang ZHANG ; Xiaowei ZHANG ; Jiangyan XU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):56-64
ObjectiveTo investigate the mechanism of salvianolic acid F (Sal F) in repairing the high glucose-induced injury in human kidney-2 (HK-2) cells via the B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/cysteinyl aspartate-specific proteinase 3 (Caspase-3)/gasdermin-E (GSDME) pathway. MethodThe cell counting kit-8 (CCK-8) was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations (2.5, 5, 10, 20 μmol·L-1) of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase (LDH) and interleukin-1β (IL-1β) in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay (ELISA) kit, respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide (PI) and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax, Bcl-2, cytochrome C, cysteinyl aspartate-specific proteinase (Caspase)-9, Caspase-3, and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2,7-dichlorodihydrofluorescein diacetate fluorescence probe (DCFH-DA) and mitochondrial membrane potential assay kit (JC-1) were used to determine the production of reactive oxygen species (ROS) and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group, the model group showed decreased cell viability (P<0.01), elevated levels LDH and IL-1β, increased proportion of PI-positive cells (P<0.01), up-regulated protein levels of Bax, cytochrome C, Caspase-9, Caspase-3, and GSDME (P<0.01), down-regulated protein level of Bcl-2 (P<0.01), decreased mitochondrial membrane potential, and excessive ROS accumulation. Compared with the model group, Sal F repaired the high glucose-induced injury in HK-2 cells (P<0.05), lowered the levels of LDH and IL-1β (P<0.05, P<0.01), and decreased the proportion of PI-positive cells (P<0.01). In addition, Sal F down-regulated the protein levels of Bax, cytochrome C, Caspase-9, Caspase-3, and GSDME and up-regulated the protein level of Bcl-2 (P<0.05, P<0.01), increased the mitochondrial membrane potential, and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS, restore the balance of mitochondrial membrane potential, and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.