冬凌草甲素抑制NF-KB、p65活化对糖尿病肾病幼龄大鼠肾损伤和免疫紊乱的影响
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陕西省科学技术计划项目(2016K14G3)


Effect of oridonin on renal injury and immune disorder in diabetic nephropathy young rats by inhibiting activation of NFKB p65
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    【摘要】目的 探讨冬凌草甲素(Ori)对糖尿病肾病(DN)幼龄大鼠的保护作用。方法 将50只SPF级大鼠随机分为对照组、模型组、DN+ Ori (5mg/kg)组、DN+ Ori (10mg/kg)组及DN+ Ori (20mg/kg)组5组,每组10只,采用高脂喂食结合化学诱导法建立糖尿病大鼠模型。留取24h尿液检测尿蛋白含量,取血检测血清肌酸酐(SCr)和尿素氮(UN);苏木精伊红(HE)和末端标记法(TUNEL)染色观察肾脏病理情况;Western blot检测半胱氨酸天冬氨酸蛋白酶3(Caspase3)、Caspase9、B细胞淋巴瘤因子2(Bcl2)和Bcl2相关X蛋白(Bax)及核因子κB p65(NFκB p65)、巨噬细胞炎性蛋白2(MIP2)的表达; ELISA检测血清中炎症相关因子白介素4(IL4)、IL6、IL10和肿瘤坏死因子(TNFα)的表达水平。结果与对照组相比,冬凌草甲素能降低模型大鼠尿蛋白、血清肌酐和尿素氮的含量(P<0.05);改善肾组织病理损伤、降低细胞凋亡率(P<0.05);下调Caspase3、Caspase9和Bax表达,上调Bcl2表达(P<0.05);抑制促炎因子IL6和TNFα表达,增强抗炎因子IL4和IL10表达(P<0.05);抑制炎症通路蛋白NFκB p65和MIP2的蛋白表达(P<0.05)。结论 冬凌草甲素通过抑制NFκB p65的活化而缓解糖尿病肾病大鼠肾损伤和免疫紊乱。

    Abstract:

    【Abstract】Objective To study the protective effect of oridonin (Ori) on diabetic nephropathy (DN) rats.Methods Rats were randomly divided into Control group, DN model group, DN+Ori (5 mg/kg), DN+Ori(10 mg/kg) and DN+Ori (20 mg/kg) group. The diabetic rat model was established by highfat diet combined with chemical induction. 24 hours urine was collected to detect urinary protein content, blood was taken to detect serum creatinine (SCr) and urea nitrogen (UN). Hematoxylineosin (HE) and TUNEL staining were used to observe renal pathology. Western blot was used to detect the expression of apoptosisrelated proteins Caspase3, Caspase9, B cell lymphoma factor2 (Bcl2), Bcl2related X protein (Bax) and inflammatory pathway NFkappa B p65, MIP2. ELISA was used to detect the expression of IL1beta, IL6 and TNFalpha in serum. Results Comparing with the control group, Ori could reduce the content of urinary protein, serum creatinine and urea nitrogen in DN model mouse (P<005), improve the pathological damage of kidney tissue and reduce the apoptotic rate (P<005), downregulate the expression of Caspase3, Caspase9 and Bcl2, upregulate the expression of Bax (P<005), inhibit the expression of inflammatory factors IL6 and TNFalpha, increase IL4 and IL10 (P<005). At the same time, Ori could inhibit the protein expression of NFkappa B 65 and MIP2 (P<005). Conclusion Ori can alleviate renal injury and immune disorder in diabetic nephropathy rats by inhibiting the activation of NFkappa B p65.

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  • 在线发布日期: 2019-11-13
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