上中下通用痛风方通过MEK/ERK/Nrf2通路改善尿酸性肾病大鼠肾纤维化OA

Objective To investigate the effect of Shang-Zhong-Xia Tongyong Tongfeng Formula on renal fibrosis in rats with uric acid nephropathy(UAN)by regulating MEK/ERK/Nrf2 signaling through inhibiting MEK/ERK and activating Nrf2.Methods Male Sprague-Dawley rats were randomized into control,UAN,gout formula,MEK inhibitor(PD98059),and gout formula+MEK activator(PMA)groups;the UAN model was established in all groups except the control group using adenine and potassium oxonate,and renal function,histopathology,fibrosis-related proteins,oxidative stress,and MEK/ERK/Nrf2 pathway levels were assessed using automated biochemistry analyzers,HE staining,Masson staining,PAS staining,immunohistochemistry,DHE staining,ELISA,and Western blot,respectively.Results Compared with control group,the UAN group showed significant upregulation of renal index,serum uric acid(SUA),serum creatinine(Scr),and blood urea nitrogen(BUN)levels,as well as renal tissue inflammatory infiltration,fibrosis area,PAS-positive area,α-SMA,TGF-β1,Collagen Ⅰ expression,reactive oxygen species(ROS),malondialdehyde(MDA),p-MEK1/2/MEK1/2,p-ERK1/2/ERK1/2(P<0.05);downregulation of superoxide dismutase(SOD),heme oxygenase-1(HO-1),and Nrf2(P<0.05).Compared with UAN group,both the gout formula and PD98059 groups significantly improved the aforementioned indices(P<0.05);compared with gout formula group,the gout formula+PMA group partially reversed these therapeutic effects(P<0.05).Conclusions Shang-Zhong-Xia Tongyong Tongfeng Formula alleviates renal fibrosis and oxidative stress in UAN rats by inhibiting MEK/ERK signaling and activating Nrf2.