黄芩苷调控氧化应激治疗糖尿病肾病OACSTPCD
Baicalin regulates oxidative stress to prevent and treat diabetic nephropathy
观察黄芩苷对糖尿病肾病(DN)小鼠的治疗作用,并探讨其可能的作用机制,将C57BL/6 小鼠 40 只随机分成5 组,每组8 只.除正常组外,其余组均采用高脂饮食(HFD)和腹腔注射链脲佐菌素(STZ)联合建模.黄芩苷低、中和高剂量组分别每天给予 100、200 和 400 mg/kg黄芩苷进行干预,正常组和模型组给予等量的生理盐水.16 周后,所有小鼠测空腹血糖浓度,称质量,测量 24h排尿量和尿白蛋白排泄率(UAE);经全自动生化分析仪检测丙二醛(MDA)、过氧化氢酶(CAT)、血清尿素氮(BUN)和血肌酐(Scr)的含量;取小鼠肾脏,计算肾指数,进行苏木精-伊红(HE)染色、过典酸雪夫氏(PAS)及马松(Masson)染色;采用免疫组化法检测叉头转录蛋白O3a(FOXO3a)和 8-羟基脱氧鸟苷(8-OHdG)的表达;采用聚合酶链式反应(PCR)检测过氧化氢酶(CAT)和锰超氧化物歧化酶(Mn-SOD)m RNA的表达;western blotting法检测肾脏组织FOXO3a蛋白表达.结果表明:经黄芩苷干预之后,DN小鼠空腹血糖明显降低,MDA含量降低,CAT含量升高,BUN和 Scr明显降低(P<0.01),24 h排尿量和UAE减少(P<0.01);染色结果也显示,黄芩苷组系膜细胞增生和纤维化程度得到改善;8-OHdG表达减少,FOXO3a表达增多;western blotting显示与模型组相比,黄芩苷组 FOXO3a蛋白表达增加;CAT和 Mn-SOD的m RNA表达量也明显增多(P<0.05).黄芩苷可有效降低血糖,减轻肾脏组织损伤,改善肾功能,治疗DN,其可能是通过激活FOXO3a,降低MDA和 8-OHdG的表达,增加CAT和Mn-SOD的表达,清除氧自由基,减轻氧化应激,从而维持内环境平衡.
This work was to explore the therapeutic effects of baicalin on mice with diabetic nephropathy and its possible mechanism.40 C57BL/6 mice were randomly divided into 5 groups,with 8 mice in each group.Except the control group,high fat diet and STZ were used to establish the mice model with diabetic nephropathy.Baicalin was administered at 100,200 and 400 mg/kg/day in low,medium and high dose groups,respectively.Meanwhile,the control and model groups were dosed with the same amount of saline.After 16 weeks,fasting blood glucose,weight,24 h urine volume and urinary albumin excretion rate(UAE)were detected,and the contents of Malondialdehyde(MDA),Catalase(CAT),blood urea nitrogen(BUN)and serum creatinine(Scr)were measured by automatic biochemical analyzer;the tissues were stained by HE,PAS and Masson.In addition,the expression of 8-OHdG and FOXO3a were analyzed by immunohistochemistry,and the expression of CAT m RNA and Mn-SOD m RNA was detected by real-time quantitative PCR,the expression of FOXO3a protein in reval tissues was detected by western blotting.As a result,the treatment with baicalin led to the decrease of the fasting blood glucose,renal index,MDA content,BUN and Scr,24 h urine and UAE,while the CAT contents increased(P<0.01,P<0.05).Based on the staining experiments,the proliferation and fibrosis of Mesangial cells were improved in baicalin groups,as well as the hyperemia and edema.Moreover,the infiltration of inflammatory cells decreased after baicalin treatment.The decrease of 8-OHdG expression and increase of FOXO3a expression were observed,along with the higher levels for m RNA expression of CAT and Mn-SOD(P<0.05).Western blotting analysis showed higher expression of FOXO3a protein compared with the model group.Overall,baicalin could effectively reduce blood sugar,alleviate renal tissue injury,improve renal function,prevent and treat diabetic nephropathy.Regarding its mechanism of action,the treatment with baicalin could activate the FOXO3a signaling,leading to the reduction of MDA and 8-OHdG expression,along with higher CAT and Mn-SOD expression.The scavenging of oxygen free radicals could maintain the balance of oxidative stress levels in the body.
郗有丽;王敏;周杰
南京大学医学院附属鼓楼医院 药学部,江苏 南京 210008江苏卫生健康职业学院 药学院,江苏 南京 211800
药学
黄芩苷糖尿病肾病叉头转录蛋白O3a过氧化氢酶锰超氧化物歧化酶
baicalindiabetic nephropathy(DN)FOXO3aCATMn-SOD
《生物加工过程》 2024 (004)
419-425 / 7
国家自然科学基金青年基金(81703577);江苏省中西医协同发展项目(CZXM2022110)
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