安徽医科大学第一附属医院肾脏内科;
目的 探讨汉黄芩素(WOG)对脂多糖(LPS)诱导的急性肾损伤的保护作用。方法 用LPS试剂诱导C57BL/6J小鼠构建脓毒症致急性肾损伤模型。以未经处理的C57BL/6小鼠作为常规对照组。24只小鼠被随机分配到四个组别：常规对照(NC)组、WOG(WOG 12.5 mg/kg)组、LPS(LPS 10 mg/kg)组以及LPS+WOG(LPS 10 mg/kg+WOG 12.5 mg/kg)组。检测小鼠血肌酐(CRE)和尿素氮(BUN)水平。聚合酶链式反应(PCR)检测小鼠肾损伤分子1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的表达情况。苏木精-伊红(HE)染色和糖原(PAS)染色观察肾脏病理损伤程度。免疫组化检测肾组织的炎性标志物白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的表达程度。Western blot法检测肾脏组织核因子κB(NF-κB)信号通路亚基P65和PP65蛋白表达变化的情况。结果 相较于NC组，LPS组CRE和BUN上升(F_(CRE)=60.90,P<0.001;F_(BUN)=82.13,P<0.001);相较于LPS组，LPS+WOG组CRE和BUN降低(P<0.001)。PCR检测结果显示，相对于NC组，LPS处理的小鼠其肾脏内的KIM-1和NGAL mRNA表达增加(F_(KIM-1)=146.3,F_(NGAL)=161.2,均P<0.001),而在LPS+WOG组中，KIM-1和NGAL mRNA表达下降(均P<0.01)。肾脏组织病理学检查显示，与NC组相比，LPS组小鼠肾组织肾小管扩张明显、炎症细胞浸润；与LPS组相比，LPS+WOG组肾小管扩张数量减少和炎症细胞浸润减少(F_(HE)=721.4,F_(PAS)=518.9,P<0.001)。免疫组化染色检测结果显示，相较于NC组，LPS处理的小鼠中IL-1β、IL-6及TNF-α的表达量上升(F_(IL-1β)=114.6,F_(IL-6)=108.9,F_(TNF-α)=251.6,均P<0.001);而对比LPS组，LPS+WOG组中的这些指标则有所减少(均P<0.01)。使用Western blot方法进一步研究表明，相较于NC组，LPS处理的小鼠其NF-κB信号途径已被激活并产生高磷酸化状态(F_(PP65)=13.02,P<0.01),然而对比LPS组时，LPS+WOG组的该路径却表现出相反的效果，即活性减弱且磷酸化程度降低(P<0.01)。结论 WOG能有效地阻断LPS引发的急性肾损伤模型小鼠的NF-κB信号途径，从而削弱由LPS引起的急性肾损伤小鼠肾脏的炎性应答及其组织损害。
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2024.08.018
中图分类号:R285.5
引用信息:
[1]王锦妮,汪靓婧,王美茜等.汉黄芩素对脂多糖诱导的急性肾损伤小鼠的保护作用[J].安徽医科大学学报,2024,59(08):1411-1416.DOI:10.19405/j.cnki.issn1000-1492.2024.08.018.
基金信息:
安徽省自然科学基金(编号：1908085MH245)