基于TLR4/BAFF/APRIL信号通路探讨肾炎止血丸对IgA肾病大鼠的作用机制  

Study on Mechanism of Shenyan Zhixue Pill(肾炎止血丸)on IgA Nephropathy Rats Based on TLR4/BAFF/APRIL Signaling Pathway

作　　者：陈明 闫晓明 王海艳 尚国旗 李莲花 程楚楚 陈瑶 张佩青 CHEN Ming;YAN Xiaoming;WANG Haiyan;SANG Guoqi;LI Lianhua;CHENG Chuchu;CHEN Yao;ZHANG Peiqing(Heilongjiang Academy of Chinese Medicine Sciences,Harbin,Heilongjiang 150036)

机构地区：[1]黑龙江省中医药科学院,黑龙江哈尔滨150036

出　　处：《中国中医药科技》2023年第6期1061-1066,共6页Chinese Journal of Traditional Medical Science and Technology

基　　金：黑龙江省中医药科研项目(ZHY2022-076);黑龙江省自然科学基金资助项目(LH2021H070)。

摘　　要：目的:观察肾炎止血丸对IgA肾病(IgAN)模型大鼠的治疗作用及其对TLR4/BAFF/APRIL通路的影响。方法:采用“牛血清白蛋白+四氯化碳+脂多糖”联用法构建IgAN大鼠模型,48只大鼠随机分为正常对照组、模型组、氯沙坦钾片组[20 mg/(kg·d)]、肾炎止血丸高剂量组[3.6 g/(kg·d)]、中剂量组[1.8 g/(kg·d)]、低剂量组[0.9 g/(kg·d)],每组8只,均连续给药6周。留取尿液、血液、肾组织标本,分别进行尿红细胞计数、尿白蛋白检测;ELISA法检测大鼠血清Toll样受体4(TLR4)、核因子κB(NF-κB)、B细胞活化因子(BAFF)、增殖诱导配体(APRIL)、核心1β1,3半乳糖基转移酶伴侣蛋白(Cosmc)、半乳糖缺陷型IgA1(Gd-IgA1)、白介素6(IL-6)水平;光镜观察各组大鼠肾组织病理变化。结果:①尿红细胞、尿蛋白变化:与模型组比较,各给药组减少明显(均P<0.01);与阳性组组比较,肾炎止血丸中剂量组、高剂量组减少明显(均P<0.01);与低剂量组比较,肾炎止血丸中剂量组、高剂量组减少明显(均P<0.01)。②TLR4、NF-κB、BAFF、APRIL、Cosmc、Gd-IgA1、IL-6:与模型组比较,各给药组TLR4、NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01);与阳性组比较,肾炎止血丸低剂量组NF-κB、BAFF减少明显(均P<0.01),中剂量组TLR4、Gd-IgA1减少(均P<0.05)及IL-6减少明显(P<0.01),高剂量组TLR4、NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01);与低剂量组比较,中剂量及高剂组TLR4、NF-κB、Gd-IgA1、IL-6减少明显(均P<0.01),中剂量组BAFF减少明显(P<0.01),高剂量组BAFF减少(P<0.05),高剂量组APRIL减少明显(P<0.01)及Cosmc升高明显(P<0.01);与中剂量组比较,高剂量组治疗后NF-κB、BAFF、APRIL、Gd-IgA1、IL-6减少明显(均P<0.01),Cosmc升高明显(P<0.01)。③病理学变化:与模型组比较,各给药组IgA、C3的免疫荧光累积光密度值(IOD)减少明显(均P<0.01);与阳性组比较,高剂量组C3 Objective:To observe the therapeutic effect of Shenyan Zhixue Pill on IgA nephropathy model rats,and to explore its mechanism based on TLR4/BAFF/APRIL pathway.Methods:Bovine serum albumin+carbon tetrachloride+lipopolysaccharide was used to construct IgAN rat model.48 rats were randomly divided into normal control group,model group,Shenyan Zhixue Pill high-dose group[3.6 g/(kg·d)],medium-dose group[1.8 g/(kg·d)],low-dose group[0.9 g/(kg·d)]and Losartan potassium tablet group[20 mg/(kg·d)],with 8 rats in each group.All of them were given the corresponding distilled water or medicines conti-nuously for 6 weeks.Urine,blood and kidney tissue were collected,urine red blood cell count and urine albumin quantitative detection,respectively.ELISA was used to determine the levels of serum TLR4,BAFF,APRIL,C1GALT1,Cosmc,Gd-IgA1 and IL-6.The pathological changes of renal tissue in each group was observed by light microscope.Results:①Changes of urine red blood cells and urine protein:Compared with model group,there were significant decreased in each medication group(all P<0.01);compared with positive group,those in the medium and high dose group of Shenyan Zhixue Pills were decreased significantly(P<0.01 for all);compared with the low dose group,those in the medium and high dose group were significantly reduced(both P<0.01).②Serum TLR4,NF-κB,BAFF,APRIL,Cosmc,Gd-IgA1,IL-6:Compared with model group,serum TLR4,NF-κB,BAFF,APRIL,Gd-IgA1 and IL-6 levels in each medication group were significantly decreased(all P<0.01),while Cosmc was significantly increased(P<0.01);compared with the positive group,NF-κB and BAFF in the low-dose group were significantly decreased(all P<0.01),TLR4,Gd-IgA1 and IL-6 in the medium-dose group were significantly decreased(all P<0.05),TLR4,NF-κB,BAFF,APRIL,Gd-IgA1 and IL-6 in high dose group were significantly decreased(all P<0.01),while Cosmc was significantly increased(P<0.01);compared with low dose group,TLR4,NF-κB,Gd-IgA1 and IL-6 in medium dose and high dose groups were significantly decrea

关 键 词：肾炎止血丸 IGA肾病 TLR4 BAFF APRIL C1GALT1 Cosmc Gd-IgA1 IL-6 病理学 大鼠 

分 类 号：R285.5[医药卫生—中药学]