摘要
目的基于磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/叉头框转录因子O亚族1(FoxO1)信号通路探究补阳还五汤对痛风模型大鼠滑膜组织细胞凋亡及炎症反应的影响。方法大鼠分为对照组(灌胃生理盐水)、痛风组(建模+灌胃生理盐水)、西药组(建模+灌胃20 mg/kg苯溴马隆)、补阳还五汤低、高剂量组(建模+灌胃6.5、26.0 g/kg补阳还五汤)和通路激活组(建模+灌胃26.0 g/kg补阳还五汤+腹腔注射0.02 mg/kg PI3K活化物(740Y-P))。测量大鼠关节肿胀度,测定血清尿酸、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,对滑膜组织进行HE染色及TUNEL检测,测定滑膜组织中p-PI3K/PI3K、pAKT/AKT、p-FoxO1/FoxO1、Caspase-3蛋白表达水平。结果与对照组相比,痛风组大鼠关节肿胀度及血清尿酸、TNF-α、IL-1β水平及滑膜组织中p-PI3K/PI3K、p-AKT/AKT、p-FoxO1/FoxO1蛋白表达水平显著升高(P<0.05),滑膜组织中细胞凋亡率及Caspase-3蛋白表达水平显著降低(P<0.05);与痛风组相比,西药组、补阳还五汤低、高剂量组大鼠关节肿胀度及血清尿酸、TNF-α、IL-1β水平及滑膜组织中p-PI3K/PI3K、p-AKT/AKT、p-FoxO1/FoxO1蛋白表达水平显著降低(P<0.05),滑膜组织中细胞凋亡率及Caspase-3蛋白表达水平显著升高(P<0.05);与补阳还五汤高剂量组相比,通路激活组大鼠关节肿胀度及血清尿酸、TNF-α、IL-1β水平及滑膜组织中p-PI3K/PI3K、p-AKT/AKT、p-FoxO1/FoxO1蛋白表达水平显著升高(P<0.05),滑膜组织中细胞凋亡率及Caspase-3蛋白表达水平显著降低(P<0.05)。结论补阳还五汤可能通过抑制PI3K/AKT/FoxO1信号通路激活,抑制炎症反应,进而促进滑膜组织细胞凋亡,改善急性痛风性关节炎大鼠症状。
This study was performed to explore the effect of Buyang Huanwu Decoction on the apoptosis of synovial tissue cells and inflammatory response in rats with gout based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/forkhead box transcription factor O1(FoxO1)signaling pathway.Rats were divided into control group(gavage of normal saline),gout group(modeling+gavage of normal saline),western medicine group(modeling+gavage of 20 mg/kg benzbromarone),Buyang Huanwu Decoction low-and high-dose groups(modeling+gavage of 6.5,26.0 g/kg Buyang Huanwu Decoction)and pathway activation group(modeling+gavage of 26.0 g/kg Buyang Huanwu Decoction+intraperitoneal injection of 0.02 mg/kg PI3K activator(740Y-P)).The degree of joint swelling in rats was measured;the levels of serum uric acid,tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)were determined;HE staining and TUNEL wereperformed on synovial tissue;and the protein expressionlevels of p-PI3 K/PI3 K,p-AKT/AKT,p-Fox O1/Fox O1,and Caspase-3 in synovial tissue were measured.Compared with the control group,the joint swelling degree,the levels of uric acid,TNF-α,IL-1βin serum and the expression levels of p-PI3 K/PI3 K,p-AKT/AKT,p-Fox O1/Fox O1 proteins in the synovial tissue of the gout group were significantly increased(P<0.05),while theapoptosis rate and the expression level of Caspase-3 protein in synovial tissue were significantly reduced(P<0.05).Compared with the gout group,the joint swelling degree,the levels of uric acid,TNF-α,IL-1βin serum and theexpression levels of p-PI3 K/PI3 K,p-AKT/AKT,p-Fox O1/Fox O1 proteins in the synovial tissue of the westernmedicine group and the Buyang Huanwu Decoction low-and high-dose groups were significantly reduced(P<0.05),while the apoptosis rate and the expression level of Caspase-3 protein in synovial tissue were significantly increased(P<0.05).Compared with the Buyang Huanwu Decoction high-dose group,the joint swelling degree,the levels of uricacid,TNF-α,IL-1βin serum and the expression levels of p-PI3 K/PI3 K,p-AKT/AKT,p-Fox O1/Fox O1 proteins inthe synovial tissue of the pathway activation group were significantly increased(P<0.05),while the apoptosis rate andthe expression level of Caspase-3 protein in synovial tissue were significantly reduced(P<0.05).Taken together,BuyangHuanwu Decoction may inhibit the activation of PI3 K/AKT/Fox O1 signaling pathway,thereby inhibiting inflammatoryresponse,promoting the apoptosis of synovial tissue cells,improving symptoms of acute gouty arthritis rats.
作者
王峰
张安兵
WANG Feng;ZHANG Anbing(Depart merit of Rheumatology and Immunology,Xiangyang Central Hospital,Xiangyang 44102 L China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2022年第7期612-619,共8页
Immunological Journal
基金
湖北省高等学校优秀中青年科技创新团队计划(T201715)。
