中华移植杂志（电子版）
中華移植雜誌（電子版）
중화이식잡지（전자판）
Chinese Journal of Transplantation(Electronic Version)
2011年
3期
7-10
,共4页
林淼%杨橙%邱月%赵天%薛寅佳%许明%戎瑞明%朱同玉
林淼%楊橙%邱月%趙天%薛寅佳%許明%戎瑞明%硃同玉
림묘%양등%구월%조천%설인가%허명%융서명%주동옥
小鼠%雷帕霉素%肾%缺血再灌注损伤
小鼠%雷帕黴素%腎%缺血再灌註損傷
소서%뢰파매소%신%결혈재관주손상
Mice%Rapamycin%Kidney%Ischemia-reperfusion injury
目的 研究雷帕霉素对肾缺血再灌注(IR)后不同时期肾小管上皮细胞凋亡及增殖、修复的影响.方法 体质量为25～30 g BALB/c小鼠45只随机分为手术对照组、IR对照组和雷帕霉素组.建立阻断小鼠左侧肾蒂30 min后切除右侧肾模型.雷帕霉素组术前及术后每日给予0.5mL雷帕霉素和生理盐水混悬液(1 mg∶10mL)灌胃,IR对照组给予等量生理盐水灌胃.术后1、3和7d每组各处死5只小鼠取全血及肾组织,检测血清肌酐水平,HE染色评价组织病理学改变.采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测肾小管上皮细胞凋亡,通过免疫组织化学检测肾小管上皮细胞增殖细胞核抗原以比较组间肾小管上皮细胞增殖修复差异.结果雷帕霉素组术后1d肾功能好于IR对照组(P＜0.05),但在7d时却较IR对照组差(P＜0.05).IR对照组和雷帕霉素组术后3个时期的肾组织病理学改变均较手术对照组严重(P＜0.05),但前两组间损伤病理学评分均无明显差异(P＞0.05).术后1d和3d时,雷帕霉素组凋亡细胞数明显少于IR对照组(P＜0.05).术后1、3和7d雷帕霉素组肾小管上皮细胞增殖细胞核抗原表达水平均显著低于IR对照组(P＜0.05).结论 肾缺血再灌注损伤早期以肾小管上皮细胞凋亡为主,后以细胞增殖修复为主.雷帕霉素因具有抗凋亡和抗增殖的双重作用,可以减轻缺血再灌注对肾功能损伤,但却不利于以后的组织修复.
目的 研究雷帕黴素對腎缺血再灌註(IR)後不同時期腎小管上皮細胞凋亡及增殖、脩複的影響.方法 體質量為25～30 g BALB/c小鼠45隻隨機分為手術對照組、IR對照組和雷帕黴素組.建立阻斷小鼠左側腎蒂30 min後切除右側腎模型.雷帕黴素組術前及術後每日給予0.5mL雷帕黴素和生理鹽水混懸液(1 mg∶10mL)灌胃,IR對照組給予等量生理鹽水灌胃.術後1、3和7d每組各處死5隻小鼠取全血及腎組織,檢測血清肌酐水平,HE染色評價組織病理學改變.採用脫氧覈糖覈苷痠末耑轉移酶介導的缺口末耑標記法檢測腎小管上皮細胞凋亡,通過免疫組織化學檢測腎小管上皮細胞增殖細胞覈抗原以比較組間腎小管上皮細胞增殖脩複差異.結果雷帕黴素組術後1d腎功能好于IR對照組(P＜0.05),但在7d時卻較IR對照組差(P＜0.05).IR對照組和雷帕黴素組術後3箇時期的腎組織病理學改變均較手術對照組嚴重(P＜0.05),但前兩組間損傷病理學評分均無明顯差異(P＞0.05).術後1d和3d時,雷帕黴素組凋亡細胞數明顯少于IR對照組(P＜0.05).術後1、3和7d雷帕黴素組腎小管上皮細胞增殖細胞覈抗原錶達水平均顯著低于IR對照組(P＜0.05).結論 腎缺血再灌註損傷早期以腎小管上皮細胞凋亡為主,後以細胞增殖脩複為主.雷帕黴素因具有抗凋亡和抗增殖的雙重作用,可以減輕缺血再灌註對腎功能損傷,但卻不利于以後的組織脩複.
목적 연구뢰파매소대신결혈재관주(IR)후불동시기신소관상피세포조망급증식、수복적영향.방법 체질량위25～30 g BALB/c소서45지수궤분위수술대조조、IR대조조화뢰파매소조.건립조단소서좌측신체30 min후절제우측신모형.뢰파매소조술전급술후매일급여0.5mL뢰파매소화생리염수혼현액(1 mg∶10mL)관위,IR대조조급여등량생리염수관위.술후1、3화7d매조각처사5지소서취전혈급신조직,검측혈청기항수평,HE염색평개조직병이학개변.채용탈양핵당핵감산말단전이매개도적결구말단표기법검측신소관상피세포조망,통과면역조직화학검측신소관상피세포증식세포핵항원이비교조간신소관상피세포증식수복차이.결과뢰파매소조술후1d신공능호우IR대조조(P＜0.05),단재7d시각교IR대조조차(P＜0.05).IR대조조화뢰파매소조술후3개시기적신조직병이학개변균교수술대조조엄중(P＜0.05),단전량조간손상병이학평분균무명현차이(P＞0.05).술후1d화3d시,뢰파매소조조망세포수명현소우IR대조조(P＜0.05).술후1、3화7d뢰파매소조신소관상피세포증식세포핵항원표체수평균현저저우IR대조조(P＜0.05).결론 신결혈재관주손상조기이신소관상피세포조망위주,후이세포증식수복위주.뢰파매소인구유항조망화항증식적쌍중작용,가이감경결혈재관주대신공능손상,단각불리우이후적조직수복.
Objective To investigate the effects of rapamycin on renal tubular epithelial cells during ischemia-reperfusion (IR) injury.Methods Forty-five male BALB/c mice ( weighing 25-30 g) were divided into 3 groups:sham,IR,and rapamycin,15 in each.IR model was made by 30 minutes of left renal ischemia with non-traumatic vascular clamps and right nephrectomy after the clamp was released.Mice in the rapamycin group were intragastrically administered with 0.5 mL suspension of rapamycin and saline ( 1 mg ∶ 1 mL) and mice in the IR group with equivalent volume of saline.Five mice were sacrificed on each time point of day 1,3,and 7 after intervention to collect blood and renal tissue samples.Serum creatinine was detected.The tissue injuries were examined by HE staining assay.Apoptosis of tubular epithelium was observed by TUNEL assay.Tubular epithelial proliferation was evaluated by assessing the expression of PCNA with immunohistochemistry.Results Serum creatinine was lower in the rapamycin group on day 1 after reperfusion [ (83.89 ± 9.53 ) μmol/L,P ＜ 0.05 ],but higher on day 7 [ ( 19.44 ± 1.15 ) μmol/L,P ＜ 0.05 ],as compared to the IR group.The IR and rapamycin groups showed more severity of tissue injuries than the sham group did (both P ＜0.05),but no significant difference was seen between the 2 groups (P ＞0.05).Less TUNEL-positive cells were observed in the rapamycin group on day 1 and 3 after reperfusion (P ＜ 0.05).The expression of PCNA in the rapanycin group was significantly decreased at all time points (P ＜ 0.05).Conclusions The apoptosis of renal tubular epithelial cells took a major part at the early stage in IR injury.However,it was replaced by cell proliferation and repair in the late period.Rapamycin attenuated renal IR injury at the early stage but delayed tubular cells repair later owing to its anti-apoptosis and anti-proliferation properties.
