长期静脉注射羧基化单壁碳纳米管对大鼠肾脏的毒性作用研究  

Toxic effect of long-term intravenous injection of carboxylated single-walled carbon nanotubes on kidney in rats

作　　者：谢雪平[1] 成晓静 秦悦[1] 李苏宁 刘华钢[1] 赖泽锋[1] Xie Xueping;Cheng Xiaojing;Qin Yue;Li Suning;Liu Huagang;Lai Zefeng(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China;Life Sciences Institute,Guangxi Medical University,Nanning 530021,China;The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region,Nanning 530023,China)

机构地区：[1]广西医科大学药学院,南宁530023 [2]广西医科大学生命科学研究院,南宁530021南宁530023 [3]广西壮族自治区妇幼保健院药剂科,南宁530023

出　　处：《广西医科大学学报》2019年第4期501-506,共6页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.21367006);广西自然科学基金资助项目(No.2012GXNSFBA053112);广西教育厅科研课题资助项目(No.200103YB024)

摘　　要：目的:评价静脉注射羧基化单壁碳纳米管(c-SWNTs)对大鼠肾脏的毒性作用。方法:将64只SD大鼠随机分为空白对照组(Control组)和实验组(c-SWNTs组),每组32只,Control组经尾静脉注射5%葡萄糖溶液,c-SWNTs组经尾静脉注射cSWNTS葡萄糖溶液。分别在干预30d、60d、90d及c-SWNTs组停止染毒30d后(共120d),每组随机取8只大鼠,麻醉处死后采集肾脏标本,透射电子显微镜(TEM)观察肾组织超微结构,苏木精—伊红(HE)染色和Masson染色观察肾组织病理学改变,Western blotting法检测Ⅲ型胶原(Col Ⅲ)蛋白的表达。结果:TEM结果显示,与Control组比较,30d后c-SWNTs组大鼠肾小球体积明显缩小,细胞核固缩,线粒体增大。HE和Masson染色结果显示,与Control组相比,c-SWNTs组大鼠肾脏血管壁局部增厚,肾小球毛细血管襻与球囊壁发生黏连,毛细血管襻内发生炎症细胞浸润,并随着染毒时间延长而向肾小球旁的间质扩散,肾小管管腔明显扩张,肾小球旁和肾髓质间质纤维组织增生;90d后c-SWNTs组大鼠肾脏炎症和纤维化程度最严重,但停止染毒30d后,炎症反应和纤维化程度有所减轻。与Control组比较,c-SWNTs组在连续染毒90d后肾组织ColⅢ蛋白表达显著上调(P<0.05),而停止染毒30d后下调,与Control组相比差异无统计学意义(P>0.05)。结论:长期静脉注射cSWNTs会损伤大鼠肾脏肾皮质、肾髓质和肾血管,引起可逆性的炎性反应和肾纤维化。Objective: To evaluate the toxic effect of long-term intravenous injection of carboxylated single-walled carbon nanotubes (c-SWNTs) on kidney in rats. Methods: Sixty-four rats were divided randomly into control group and c-SWNTs group,with 32 cases in each group.Rats in the control group were injected with 5% glucose solution via tail vein,and rats in c-SWNTs group were injected with c-SWNTS-glucose solution via tail vein.After 30 d,60 d,90 d and 120 d (90 d injection+30 d recovery) of intervention,eight rats were selected from each group and killed after anesthesia.Ultrastructure of renal tissue was observed by transmission electron microscope (TEM).Hematoxylin-eosin (HE) staining and Masson staining were used to observe pathological changes of renal tissue.Western blotting was used to detect the expression of type Ⅲ collagen (Col Ⅲ) protein. Results: After 30 days of intervention,reduced glomerular volume,karyopyknosis and swollen mitochondria were observed in the c-SWNTs group.Locally thickened renal vessels walls,glomerular capillary loop adhered to Bowman’s capsu- le,inflammatory cell infiltration in capillary loop and spread to periglomerular interstitium with the prolong of treatment time,obvious dilation of renal tubule lumen,and periglomerular and medulla interstitial fibrogenesis were found in the c-SWNTs group by HE staining and Masson staining.After 90 days,the rats in the c-SWNTs group had severest renal inflammation and fibrosis,and significantly higher protein level of Col Ⅲ compared with the control group (P<0.05).There was no significant difference in the protein expression of Col Ⅲ after 30 days of recovery between control group and c-SWNTs group (P >0.05). Conclusion: Long-term intravenous injection of c-SWNTs might lead to renal cortex,renal medulla and renal vessels injuries,and reversible inflammatory response and renal fibrosis.

关 键 词：单壁碳纳米管 静脉注射 肾脏 炎性反应 纤维化 

分 类 号：R114[医药卫生—卫生毒理学]