摘要
背景:前期实验发现干细胞对于肾纤维化的早期形成具有一定的干预作用,能够延缓肾间质纤维化的发生。目的:研究外源性脂肪干细胞移植对大鼠早期肾间质纤维化形成的影响,并探讨其量效关系。方法:将50只SD大鼠随机分为5组,假手术组尾静脉注射PBS;模型组、低剂量组、中剂量组、高剂量组结扎左侧输尿管,建立肾纤维化模型,造模成功后,模型组尾静脉注射PBS,低剂量组、中剂量组、高剂量组尾静脉分别注射细胞浓度为1×10^(10),2×10^(10),3×10^(10) L^(-1)的脂肪干细胞悬液0.1 mL。注射后14 d取左肾组织,采用苏木精-伊红染色和Masson染色观察肾小管-间质损伤程度及肾间质相对面积,免疫组织化学法检测α-平滑肌肌动蛋白和转化生长因子β1表达。结果与结论:①苏木精-伊红染色:模型组表现为典型的肾小球及肾小管-间质改变;低剂量组、中剂量组、高剂量组均有一定程度的肾小球及肾小管-间质改变,但程度较模型组明显减轻,以高剂量组损伤程度最轻;②Masson染色:模型组肾小管间质增宽,胶原纤维沉积;低剂量组、中剂量组、高剂量组肾间质增宽程度低于模型组,中、高剂量组肾间质增宽程度低于低剂量组(P<0.05);③免疫组织化学染色:与假手术组比较,模型组α-平滑肌肌动蛋白、转化生长因子β1表达升高(P<0.05);与模型组比较,高剂量组α-平滑肌肌动蛋白表达降低(P<0.05),低、中、高剂量组转化生长因子β1表达均降低(P<0.05),以中、高剂量组转化生长因子β1降低更明显;④结果表明:外源性脂肪干细胞移植可延缓早期肾纤维化的形成,并存在剂量-效应关系,其机制可能是通过改变转化生长因子β1诱导的信号通道状态实现的。
BACKGROUND:Our preliminary findings have shown that stem cells have a certain effect on early formation of renalfibrosis and delay the occurrence of renal interstitial fibrosis.OBJECTIVE:To investigate the effect of exogenous adipose-derived stem cell transplantation on the formation of renalinterstitial fibrosis in rats,and to explore the dose-effect relationship.METHODS:Fifty Sprague-Dawley rats were randomly divided into five groups.Rats in sham operation group wereinjected with PBS;and those in the other four groups were ligated to establish the model of renal fibrosis.Aftersuccessful modeling,the model group was injected with PBS,while low dose group,middle dose group and high dosegroup were injected with1×107/L,2×107/L,3×107/L adipose-derived stem cell suspension(0.1mL),respectively.Ratswere killed14days after injection.Hematoxylin-eosin staining and Masson staining were used to observe the degree ofrenal tubular interstitial injury and the relative area of the renal interstitium.Expression of alpha smooth muscle actinand transforming growth factor beta1was detected by immunohistochemistry.RESULTS AND CONCLUSION:(1)Hematoxylin eosin staining:The model group showed typical glomerular andtubulointerstitial changes;the low,middle and high dose groups had a certain degree of glomerular andtubulointerstitial changes,but the severity of injury in these three groups,especially in the high dose group,wassignificantly milder than that in the model group.(2)Masson staining:In the model group,the renal interstitium waswidened and the collagen fibers were deposited;in the low,middle and high dose groups,the degree of renal interstitialexpansion was lower than that in the model group,and moreover,the degree of renal interstitial expansion in themiddle and high dose groups was lower than that in the low dose group(P<0.05).(3)Immunohistochemical staining:Compared with the sham operation group,the expression of alpha smooth muscle actin and transforming growth factorbeta1in the model group was higher than that in the sh
作者
吕春燕
李进辉
刘伟伟
陈昌金
吴程
赵梓亦
沈东成
Lv Chun-yan;Li Jin-hui;Liu Wei Wei;Chen Chang-jin;Wu Cheng;Zhao Zi-yi;Shen Dong-cheng(Department of Pathology,Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China;College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China;Central Laboratory, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China)
出处
《中国组织工程研究》
CAS
北大核心
2017年第29期4685-4690,共6页
Chinese Journal of Tissue Engineering Research
基金
四川省卫生厅项目(110520)
成都市卫生局项目(2014004)
成都中医药大学实验技术项目(071002)~~
关键词
干细胞
纤维化
转化生长因子Β1
组织工程
Stem Cells
Fibrosis
Transforming Growth Factor beta1
Tissue Engineering
