紫草素对过敏性紫癜性肾炎小鼠肾功能、炎症及p38 MAPK/NF-κB信号通路的影响OACSTPCD
Effects of Shikonin on Renal Function,Inflammation and p38MAPK/NF-κB Signaling Pathway in Mice with Henoch-Schonlein Purpura Nephritis
目的:探讨紫草素对过敏性紫癜性肾炎(HSPN)小鼠肾功能、炎症及p38MAPK/NF-κB信号通路的影响.方法:建立HSPN小鼠模型,将造模成功小鼠随机分为模型组、环磷酰胺组(给予环磷酰胺22 mg/kg)、紫草素低剂量组(给予紫草素 5 mg/kg)、紫草素高剂量组(给予紫草素 10 mg/kg),每组12 只;另外取12 只小鼠不进行处理,正常饲养作为对照组.各组小鼠给予相应药物干预28 d.全自动生化分析仪和酶联免疫吸附法分别检测小鼠肾功能和血清炎症指标;HE染色观察肾脏组织病理学变化;荧光定量PCR和蛋白印迹法分别检测肾脏组织中p38MAPK、NF-κB mRNA和蛋白表达.结果:对照组小鼠肾脏组织肾小管及肾小球结构清晰,无炎性细胞浸润、系膜增生情况;与对照组相比,模型组小鼠出现肾脏组织炎性细胞浸润、系膜增生现象严重,肾小管萎缩,肾小球血管网结构模糊、血管充血等病理损伤,血清肌酐(SCr)、血尿素氮(BUN)、24 h尿液中尿蛋白(24 h UP)、血清白细胞介素(IL-6、IL-1β)、肿瘤坏死因子-α(TNF-α)、肾脏组织 p38MAPK、NF-κB mRNA 和蛋白表达水平升高(P<0.05);与模型组相比,环磷酰胺组、紫草素低、高剂量组小鼠肾脏组织炎性细胞浸润、肾小管上皮细胞空泡变性及肿胀等现象得到改善,SCr、BUN、24 h UP、血清IL-6、IL-1β、TNF-α、肾脏组织p38MAPK、NF-κB mRNA和蛋白表达水平降低(P<0.05);紫草素高剂量组上述指标改善效果优于紫草素低剂量组(P<0.05).结论:紫草素可改善HSPN小鼠肾功能和炎症反应,减轻肾脏病理损伤,其机制可能与抑制p38MAPK/NF-κB信号通路的激活有关.
Objective:To investigate the effects of shikonin on renal function,inflammation and p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor-κB(NF-κB)signaling pathway in mice with Henoch-Schonlein purpura nephritis(HSPN).Methods:The HSPN mice model was established,and the successful mice were randomly divided into model group,cyclophosphamide group(22 mg/kg),shikonin low dose group(5 mg/kg)and shikonin high dose group(10 mg/kg),with 12 mice in each group.In addition,12 mice were left untreated and raised normally as the control group.Each group was given corresponding drug intervention for 28 days.Automatic biochemical analyzer and enzyme-linked immunosorbent assay were used to detect renal function and serum inflammation indexes respectively;HE staining was used to observe the histopathological changes of kidney;the messenger RNA(mRNA)and protein expressions of p38MAPK and NF-κB in kidney tissues were detected by quantitative PCR and Western blotting respectively.Results:In the control group,the renal tubules and glomeruli were clear and without inflammatory cell infiltration and mesangial hyperplasia.Compared with control group,the kidney tissues of model group mice showed severe inflammatory cell infiltration,severe mesangial hyperplasia,atrophy of renal tubules,blurred glomerular vascular network structure,vascular congestion and other pathological damage,and the serum creatinine(SCr),blood urea nitrogen(BUN),24 h urine protein(24 h UP),serum interleukin(IL)-6,IL-1β,tumor necrosis factor-α(TNF-α),p38MAPK and NF-κB mRNA and protein expression levels in kidney tissue were increased(P<0.05).Compared with model group,the inflammatory cell infiltration,vacuolar degeneration and swelling of renal tubular epithelial cells were improved in kidney tissues of cyclophosphamide group and shikonin low and high dose groups,and SCr,BUN,24 h UP,serum IL-6,IL-1β,TNF-α,p38MAPK and NF-κB mRNA and protein expression levels in kidney tissues were decreased(P<0.05);the improvement effect of above indexes in shikonin high dose group was better than that in shikonin low dose group(P<0.05).Conclusion:Shikonin can improve renal function and inflammatory response and reduce renal pathological injury in HSPN mice,and the mechanism may be related to the inhibition of p38MAPK/NF-κB signaling pathway activation.
范颖;董娜;杨会慈;马靖;王云
保定市第二医院儿科,河北 保定 071052
中医学
紫草素过敏性紫癜性肾炎p38丝裂原活化蛋白激酶/核因子-κB信号通路肾功能
ShikoninHenoch-Schonlein purpura nephritisp38 mitogen-activated protein kinase/nuclear factor-κB signaling pathwayRenal function
《中医药学报》 2024 (004)
34-39 / 6
河北省中医药类科研计划项目(2021285)
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