山东医药
山東醫藥
산동의약
SHANDONG MEDICAL JOURNAL
2014年
43期
12-15
,共4页
李诚%林晓杰%陈燕燕%张丽娟%李堂
李誠%林曉傑%陳燕燕%張麗娟%李堂
리성%림효걸%진연연%장려연%리당
糖尿病%1型糖尿病%白细胞介素10%免疫疗法%非肥胖型糖尿病鼠
糖尿病%1型糖尿病%白細胞介素10%免疫療法%非肥胖型糖尿病鼠
당뇨병%1형당뇨병%백세포개소10%면역요법%비비반형당뇨병서
diabetes mellitus%type 1 diabetes mellitus%interleukin 10%immunotherapy%nonobese diabetic mouse
目的:观察腺病毒介导的IL-10(Ad-mIL-10)基因干预对1型糖尿病(T1DM)发病早期的非肥胖型糖尿病( NOD)鼠胰岛β细胞的保护作用。方法选取17~20周龄近期发病(诊断为T1DM不超过3 d)的雌性NOD小鼠12只,随机分为A、B组(各6只),A组发病后立即予腹腔注射0.1 mL的Ad-mIL-10,B组未予任何干预;另选取相同周龄未发病的NOD鼠6只为C组,未予任何干预。实验前及实验开始后的第1、2、3周记录小鼠体质量、尿糖及血糖;第3周时处死全部小鼠,摘眼球法取全血并测血清 IL-10、IFN-γ、IL-4和 C肽;取胰腺做病理切片,HE及免疫组化染色,观察小鼠胰岛炎性浸润程度及IL-10基因在胰腺的表达情况。结果与B组相比,A组胰腺局部IL-10高表达、血清IL-10水平升高(P<0.01);A组血清IFN-γ水平较B组降低、IL-4及IL-10水平较B组升高、IFN-γ/IL-4较B组降低,两组相比, P均<0.01;A组血清C肽水平较B组升高,两组相比,P<0.01。结论 Ad-mIL-10基因干预可对自然发病NOD小鼠发挥一定的免疫调节作用,一定程度上改善其胰岛β细胞功能。
目的:觀察腺病毒介導的IL-10(Ad-mIL-10)基因榦預對1型糖尿病(T1DM)髮病早期的非肥胖型糖尿病( NOD)鼠胰島β細胞的保護作用。方法選取17~20週齡近期髮病(診斷為T1DM不超過3 d)的雌性NOD小鼠12隻,隨機分為A、B組(各6隻),A組髮病後立即予腹腔註射0.1 mL的Ad-mIL-10,B組未予任何榦預;另選取相同週齡未髮病的NOD鼠6隻為C組,未予任何榦預。實驗前及實驗開始後的第1、2、3週記錄小鼠體質量、尿糖及血糖;第3週時處死全部小鼠,摘眼毬法取全血併測血清 IL-10、IFN-γ、IL-4和 C肽;取胰腺做病理切片,HE及免疫組化染色,觀察小鼠胰島炎性浸潤程度及IL-10基因在胰腺的錶達情況。結果與B組相比,A組胰腺跼部IL-10高錶達、血清IL-10水平升高(P<0.01);A組血清IFN-γ水平較B組降低、IL-4及IL-10水平較B組升高、IFN-γ/IL-4較B組降低,兩組相比, P均<0.01;A組血清C肽水平較B組升高,兩組相比,P<0.01。結論 Ad-mIL-10基因榦預可對自然髮病NOD小鼠髮揮一定的免疫調節作用,一定程度上改善其胰島β細胞功能。
목적:관찰선병독개도적IL-10(Ad-mIL-10)기인간예대1형당뇨병(T1DM)발병조기적비비반형당뇨병( NOD)서이도β세포적보호작용。방법선취17~20주령근기발병(진단위T1DM불초과3 d)적자성NOD소서12지,수궤분위A、B조(각6지),A조발병후립즉여복강주사0.1 mL적Ad-mIL-10,B조미여임하간예;령선취상동주령미발병적NOD서6지위C조,미여임하간예。실험전급실험개시후적제1、2、3주기록소서체질량、뇨당급혈당;제3주시처사전부소서,적안구법취전혈병측혈청 IL-10、IFN-γ、IL-4화 C태;취이선주병리절편,HE급면역조화염색,관찰소서이도염성침윤정도급IL-10기인재이선적표체정황。결과여B조상비,A조이선국부IL-10고표체、혈청IL-10수평승고(P<0.01);A조혈청IFN-γ수평교B조강저、IL-4급IL-10수평교B조승고、IFN-γ/IL-4교B조강저,량조상비, P균<0.01;A조혈청C태수평교B조승고,량조상비,P<0.01。결론 Ad-mIL-10기인간예가대자연발병NOD소서발휘일정적면역조절작용,일정정도상개선기이도β세포공능。
Objective To obverse the protective effect on pancreas islet βcells of nonobese diabetic ( NOD) mouse in early phase of type 1 diabetes mellitus caused by adenovirus vector-mediated murine IL-10( Ad-mIL-10) genes.Methods 12 female NOD mice of 17-20 weeks old with diagnosis of type 1 diabetes mellitus less than 3 days were collected and random-ly divided into group A and B ( 6 mice in each group ) .Mice in group A were intraperitoneal injected with Ad-mIL-10 (0.1 mL) immediately in the early stage of diabetes and those in group B were treated with nothing as control .In addition, 6 NOD mice which in same age range and at inactive stage of disease were selected as group C , without any intervention .Data of weight, urine and blood sugar of mice at 4 time points which before the trial and 1, 2, 3 weeks after beginning were recor-ded for analysis .All mice were condemned to death in the third week , and whole blood was collected by method of picking eyeball, which then was used for measurement of IL-10, IFN-γ, IL-4 and C-peptide in blood serum.Several pathological sec-tions from pancreas which stained with HE and Immunohistochemistry assay were collected to analyze the infiltration degree of pancreas islet and expression of IL-10 genes in pancreas .Results Compared with group B , group A showed high IL-10 ex-pression in local pancreas and increased IL-10 figures in blood serum(P<0.01).In group A, the data of measured IFN-γand IFN-γ/IL-4 were lower than those of group B , whereas, IL-4 and IL-10 were detected in higher expression ( all P<0.01).C-peptide level in serum was more significant in group A (P<0.01).Conclusions IL-10 gene intervention has an immunomodulatory role on spontaneous disease of NOD mice .It can improve the function of islet beta cells to a certain ex-tent, but has no effect on insulitis alleviation and blood glucose control .