加味当归补血汤对糖尿病肾病大鼠AMPK及PGC-1α的影响及相关作用机制  

Effect and mechanism of Modified Danggui Buxuetang on AMPK and PGC-1αin diabetic kidney disease rats

作　　者：丁鑫 顾悦 王逸凡 申宇航 张宇翔 郭登洲 DING Xin;GU Yue;WANG Yifan;SHEN Yuhang;ZHANG Yuxiang;GUO Dengzhou(Graduate School,Hebei University of Chinese Medicine,Shijiazhuang 050200,Hebei,China;Department of Gastroenterology,the Third Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei,China;The Second Department of Nephrology,the First Affiliated Hospital of Hebei University of Chinese Medicine,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,Hebei,China)

机构地区：[1]河北中医学院研究生学院,河北石家庄050200 [2]河北医科大学第三医院消化内科,河北石家庄050000 [3]河北中医学院第一附属医院∥河北省中医院肾二科,河北石家庄050011

出　　处：《暨南大学学报（自然科学与医学版）》2023年第2期147-156,185,共11页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家中医临床研究基地建设项目(国中医药科技函[2018]131号);河北省自然科学基金项目(H2022423367);河北省中医药管理局科研计划项目(2021167);河北省脾肾病证中医治疗技术创新中心项目(SG2021187);政府资助临床医学优秀人才培养项目(13000022P00DE34100247)。

摘　　要：目的:观察加味当归补血汤(MDBT)对糖尿病肾病(DKD)大鼠单磷酸腺苷激活蛋白激酶(AMPK)及过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)活性的影响,探讨其治疗DKD的可能机制。方法:52只SD雄性大鼠随机分为正常组(CON)8只和造模组44只。后随机将40只成模大鼠分为模型组(MOD)、厄贝沙坦组(IRB)、加味当归补血汤高剂量组(MDBTH)、加味当归补血汤中剂量组(MDBTM)、加味当归补血汤低剂量组(MDBTL),8只/组。药物组灌相应药物,CON组予等体积生理盐水,1次/d,持续20周。检测各组大鼠24 h尿蛋白(24 h-UTP)水平、血清锰超氧化物歧化酶(MnSOD)及丙二醛(MDA)活性;观察大鼠肾组织病理变化;免疫组化法(IHC)及Western blot法检测肾组织磷酸化AMPK(p-AMPK)、PGC-1α蛋白表达。结果:与CON组比较,MOD组24 h-UTP及血清MDA水平显著升高,MnSOD活性显著降低(P<0.01);病理表现为肾小管和肾小囊严重分离,肾小球内基底膜均匀性增厚,球内糖原沉积;肾组织中p-AMPK、PGC-1α蛋白表达水平显著降低(P<0.01)。与MOD组比较,MDBTH与IRB组24 h-UTP及血清MDA水平显著下降,MnSOD活性显著提高(P<0.01);肾组织病理表现明显改善;p-AMPK、PGC-1α在肾组织的表达显著增加(P<0.01)。结论:加味当归补血汤可能通过激活AMPK及PGC-1α的表达改善DKD大鼠氧化应激,降低肾脏病理损害程度,减少蛋白尿,从而有效保护肾脏,缓解DKD进展。Objective:To observe the effects of Modified Danggui Buxuetang on the activities of adenosine monophosphate activated protein kinase(AMPK)and peroxisome proliferator-activated receptor-γ-coactivator 1-α(PGC-1α)in diabetic kidney disease(DKD)rats,and to explore the possible mechanism of its treatment for DKD.Methods:Fifty-two male SD rats were divided into normal group(CON,n=8)and rats for DKD modeling(n=44)according to random number table method.The remaining 40 DKD model rats were randomly divided into model group(MOD),irbesartan group(IRB),Modified Danggui Buxuetang high-dose group(MDBTH),Modified Danggui Buxuetang medium-dose group(MDBTM)and Modified Danggui Buxuetang low-dose group(MDBTL),8 rats in each group.The medicine groups were given the corresponding drug,and the CON groups were given the same volume of normal saline intragastrically,once a day,continuous intervention for 20 weeks.Then the 24 h urinary protein(24 h-UTP),malondialdehyde(MDA)and serum manganese superoxide dismutase(MnSOD)in rats were measured.The pathological changes of renal tissue in each group were observed.Phosphorylated AMPK(p-AMPK)and PGC-1αwere detected by immunohistochemistry(IHC)and Western blot.Results:Compared with CON group,24 h-UTP and MDA in MOD group were significantly increased,and serum MnSOD was significantly decreased(P<0.01).The pathological findings were severe separation of renal tubules from renal capsules,obvious uniform thickening of glomerular basement membrane,and glycogen deposition in glomerulus.The expression of p-AMPK and PGC-1αin kidney tissue decreased significantly(P<0.01).Compared with MOD group,24 h-UTP and serum MDA in MDBTH and IRB groups were significantly decreased,and MnSOD was significantly increased(P<0.01).Renal histopathology improved significantly.The expressions of p-AMPK and PGC-1αin renal tissue were significantly increased(P<0.01).Conclusion:Modified Danggui Buxuetang may improve the oxidative stress of DKD rats by activating the expression of AMPK and PGC-1α,and then reduce renal

关 键 词：加味当归补血汤 糖尿病肾病(DKD) 过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α) 单磷酸腺苷激活蛋白激酶(AMPK) 氧化应激 

分 类 号：R2-0[医药卫生—中医学] R289.5