CAJ | 학술논문

目的观察HBV相关性肾炎(HBV-GN)患者肾组织Toll样受体4(TLR4)的表达及分布情况,探讨TLR4与HBV-GN肾组织病变及临床表现的关系.方法采用免疫组化法检测经肾活检确诊的48例HBV-GN患者及154例非HBV-GN患者的肾组织标本,观察肾组织TLR4的分布特征,明确TLR4与HBsAg的分布关系,结合病史资料,统计并分析其与病理类型,肾小球、肾小管病变程度,肾间质炎性细胞浸润程度及血清HBV等临床指标之间的关系.结果 TLR4以棕红色颗粒状物主要沉积在HBV-GN组患者的肾小管及间质中,且与HBsAg的分布基本一致.HBV-GN组TLR4阳性率及阳性积分均高于非HBV-GN组(P＜0.05).在系膜增生性肾小球肾炎组、局灶节段性肾小球硬化症组TLR4阳性积分略高,但差异无统计学意义(P＞0.05)；肾小管病变程度与TLR4的表达显著相关(r =0.748,P＜0.001),且随肾小管萎缩、炎性细胞浸润及间质纤维化的程度加重而升高(r分别为0.577、0.684、0.569,P值均＜0.001),但与肾小球的病变程度无显著相关性(r=0.293,P=0.053).回归分析发现,TLR4表达随血压的升高、GFR的下降、高敏C反应蛋白的增加及24h尿蛋白定量的增多而增加(R2分别为0.869、0.784、0.979、0.615),其余临床指标均无统计学意义.结论 TLR4在HBV-GN肾组织中有异常表达,主要分布于肾小管上皮细胞及间质组织,其分布与HBsAg分布基本一致,表达水平与炎性细胞浸润、肾间质病变及肾功能变化密切相关.故推测,HBV-GN肾组织中的HBV可促进TLR4的异常表达,后者可能参与了HBV-GN的肾脏组织病变的进展.
목적 관찰HBV상관성신염(HBV-GN)환자신조직Toll양수체4(TLR4)적표체급분포정황,탐토TLR4여HBV-GN신조직병변급림상표현적관계.방법 채용면역조화법검측경신활검학진적48례HBV-GN환자급154례비HBV-GN환자적신조직표본,관찰신조직TLR4적분포특정,명학TLR4여HBsAg적분포관계,결합병사자료,통계병분석기여병리류형,신소구、신소관병변정도,신간질염성세포침윤정도급혈청HBV등림상지표지간적관계.결과 TLR4이종홍색과립상물주요침적재HBV-GN조환자적신소관급간질중,차여HBsAg적분포기본일치.HBV-GN조TLR4양성솔급양성적분균고우비HBV-GN조(P＜0.05).재계막증생성신소구신염조、국조절단성신소구경화증조TLR4양성적분략고,단차이무통계학의의(P＞0.05)；신소관병변정도여TLR4적표체현저상관(r =0.748,P＜0.001),차수신소관위축、염성세포침윤급간질섬유화적정도가중이승고(r분별위0.577、0.684、0.569,P치균＜0.001),단여신소구적병변정도무현저상관성(r=0.293,P=0.053).회귀분석발현,TLR4표체수혈압적승고、GFR적하강、고민C반응단백적증가급24h뇨단백정량적증다이증가(R2분별위0.869、0.784、0.979、0.615),기여림상지표균무통계학의의.결론 TLR4재HBV-GN신조직중유이상표체,주요분포우신소관상피세포급간질조직,기분포여HBsAg분포기본일치,표체수평여염성세포침윤、신간질병변급신공능변화밀절상관.고추측,HBV-GN신조직중적HBV가촉진TLR4적이상표체,후자가능삼여료HBV-GN적신장조직병변적진전.
Objective To investigate the expression and distribution of Toll-like receptor 4 (TLR4) in renal tissue of HBV associated nephropathy (HBV-GN) and its role in the pathogenesis and clinical manifestations of HBV-GN.Methods Renal tissues were sampled from 48 HBV-GN patients confirmed by renal biopsy and 154 non-HBV-GN patients.The distribution of TLR4 in renal tissue and the relationship between the distribution of TLR4 and HBsAg were detected by immunohistochemistry.Integrating case record,correlations between the expression of TLR4 with clinical parameters including pathology,glomeruli,kidney tubules lesions,renal interstitial inflammatory infiltration and blood serum HBV were analyzed.Results TLR4 mainly distributed in the renal tubular epithelial cells and interstitial areas as brownish red and granular,which was in consistent with HBsAg distribution.The TLR4 positive rate and score in HBV-GN group were higher than those in non-HBV-GN group (P ＜ 0.05 ).TLR4 positive score was slightly higher in mesangial proliferative glomerulonephritis group and focal segmental glomerulosclerosis group,which had no significant difference (P ＞ 0.05).Kidney tubules lesions were strongly associated with TLR4 expression (r =0.748,P ＜ 0.001 ) which increased with aggravation of renal interstitial fibrosis ( r =0.569,P ＜0.001 ),tubular atrophy ( r =0.577,P ＜ 0.001 ) and inflammatory cell infiltration ( r =0.684,P ＜0.001 ).No obvious correlation with glomeruli lesions was observed ( r =0.293,P =0.053 ).Negative correlation could be seen between TLR4 and the renal function ( R2 =0.784),systolic blood pressure ( R2 =0.869),high sensitivity C-reactive protein (R2 =0.979) and urinary protein (R2 =0.615 ) by regression analysis.Other clinical parameters had no statistical significances.Conclusions The expression of TLR4 is abnormal in the renal tissue of HBV-GN patients,mainly in renal tubular epithelial cells and interstitial,which is consistent with the distribution of HBsAg.Its intensity is closely related with renal interstitial lesions,renal function changes and inflammatory cell infiltration.A speculation,that HBV can promote abnormal expression of TLR4 in renal tissues of HBV-GN which may be involved in the lesion progress of HBV-GN,is made upon our study.