马兜铃酸Ⅰ对大鼠体内PI3K/Akt/NF-кB通路的影响к

Effect of Aristolochic AcidⅠ on PI3K/Akt/NFкB Signaling Pathway in Rats

目的探讨马兜铃酸Ⅰ(Aristolochic acidⅠ,AAⅠ)诱导的马兜铃酸肾病可能病变机制,分析其对PI3K/Akt/NFкB通路的影响。方法 SD雄性大鼠按随机数字表法分为空白对照组以及AAⅠ高、低剂量(9.0、2.25mg/kg)组,连续腹腔注射给药14d后,取血清检测肌酐(Cr)、尿素氮(BUN)、碱性磷酸酶(AKP),并用HE法染色观察肾脏病理组织学变化;用蛋白免疫印迹(Western blot)法分析PI3K、Akt、NFкB蛋白的表达,此外用免疫组织化学方法分析AAⅠ对肾脏组织IL-6和TNF-的表达变化。结果给药AAⅠ组与对照组比较,Cr、BUN、AKP水平显著升高(P<0.05);肾脏病理学检查显示肾脏病变和炎症改变,IL-6、TNF-表达显著增多(P<0.01);PI3K、Akt、NFкB及其磷酸化蛋白表达水平增高。结论 AAⅠ能导致肾脏毒性,并且可能通过激活PI3K/Akt/NFкB通路,诱发炎症,从而加重肾脏组织病理学改变。

ABSTRACT：OBJECTIVE To investigate the potential mechanism of aristolochic acid Ⅰ（AAⅠ）on aristolochic acid nephrop-athy and the effect of AAⅠ on PI3K/Akt/NF-κB signaling pathway in rats.METHODS 27 male SD rats were randomly di-vided into three groups：control group,AAⅠ low-dose group（2.25 mg/kg） and AAⅠ high-dose group （9.0 mg/kg）.Rats were intraperitoneally injected with AAⅠ once daily for 14 d.Then the serum were taken to determine the content of Cr,BUN and AKP in rats;renal pathological changes were examined by HE staining;the expression levels of PI3K,Akt,NF-κB were analyzed by Western blot;the expression changes of IL-6 and TNF-αwere detected by immunohistochemical assay.RESULTS Compared with control group,the levels of Cr,BUN and AKP in AAⅠ groups were increased significantly（P 〈0.05）;kidney pathological examination revealed the improvement of kidney disease and inflammation;the expressions of IL-6 and TNF-αwere increased significantly（P 〈0.01）;the expression of PI3K,Akt and NF-κB were up-regulated.CONCLUSION AAⅠ can induce the kidney injury and inflammation and activate the PI3K/Akt/NF-κB signaling pathway,thus worsen patho-logical changes of kidney tissue.