缺血预处理对肝脏缺血再灌注损伤的保护机理研究
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摘要
目的：研究缺血预处理对大鼠肝脏缺血再灌注损伤保护作用
机制；绘制缺血再灌注后0—48h各损伤指标与抗损伤因素的
变化曲线，并与缺血预处理后的指标变化进行对比；预处理
的延迟保护效应与热休克蛋白的关系，预处理影响下热休克
蛋白70mRNA表达水平的变化。
方法：建立大鼠肝脏缺血再灌注模型并进行缺血预处理，实
验分组如下①假手术组(Sham-operation, S组）、②缺血再灌
注组（Ischemic Reperfusion, I/R组）、③缺血预处理组（Ischemic
Preconditioning, PC组）、④预处理加左旋硝基精氨酸组
（Preconditioning+L-NNA, PC+L组），各组再灌注后检测血清
丙氨酸转氨酶（ALT）及丙二醛（MDA）含量、热休克蛋白
70（HSP70）免疫组化染色及mRNA检测，肝组织石蜡切片HE
染色及电镜观察；结果：PC组ALT及MDA含量明显低于
I/R组（p＜0.01），肝组织损伤程度明显减轻；PC+L组在0—
3h阶段ALT和MDA含量与I/R组无显著区别（p＞0.05），而
在6—48h阶段则显著低于I/R组（p＜0.01）但仍高于PC组
（p＜0.05）。HSP70免疫组化染色：PC组、PC+L组3—48h
染色阳性率逐渐增多并显著高于I/R组（p＜0.01）；
第四军医大学98年级硕士学位论文
HSP70W表达逐渐增高，6一 12h 最高，其 PC组、PC＋L
组显著高于IR组一叩刀1人结论：缺血预处理对大鼠肝脏
缺血再灌注损伤具有明显保护作用，0—3h为早期保护效应，
可能为NO所触发或介导，6—48h为延迟保护效应（Late
Ischemic Preconditioning），HSP 70可能是导致延迟保护效应
的重要因素。
Objective: To study late preconditioning(PC) against ischemia/reperfusion(I/R) injury in rats liver. Methods 168 SD rats were divided into four groups: (1) S group: n=42,sham-operated control; (2)I/R group:n=42,Subjected to ischemic for 70-minute ischemia; (3) PC group: n=42,Two cycles of 5 min of ischemia followed by 5 min of reperfusion was performed before I/R;(4)PC+L group: n=42, L-NNA was administered before preconditioning then 70min ischemia. Followed by continuous reperfusion, serum ALT MDA NO NOS GSH GST and GSH-PX were examined in all groups during 0-48h; HSP 70 in the liver tissue were quantitatively analyzed and located by immunocytochemical technique. HSP 70 mRNA
were analyzed by PAGE Results Serum ALT and MDA in either I/R and PC+L group were markedly increased than in PC group (P<0.01) at any point after reperfusion.There is not significant difference between I/R group and P+L group during 0-3h(p>0.05) but during 6-48h(p<0.01). ALT and MDA were increased in PC+L vs PC group(p<0.05) and markedly decreased than I/R group during 6-48h(p<0.01). Expresstion of HSP 70 in PC and P+L group is gradually increased higher than in I/R group during 6-48h (P<0.01) ,so as HSP70 mRNA during l-12h.(p<0.01).Conc!usions: NO and HSP 70 might be participate in the protection against liver ischemia/reperfusion injury and NO might be protect liver in early preconditioning and HSP 70 might be associate with late preconditioning.
机制；绘制缺血再灌注后0—48h各损伤指标与抗损伤因素的
变化曲线，并与缺血预处理后的指标变化进行对比；预处理
的延迟保护效应与热休克蛋白的关系，预处理影响下热休克
蛋白70mRNA表达水平的变化。
方法：建立大鼠肝脏缺血再灌注模型并进行缺血预处理，实
验分组如下①假手术组(Sham-operation, S组）、②缺血再灌
注组（Ischemic Reperfusion, I/R组）、③缺血预处理组（Ischemic
Preconditioning, PC组）、④预处理加左旋硝基精氨酸组
（Preconditioning+L-NNA, PC+L组），各组再灌注后检测血清
丙氨酸转氨酶（ALT）及丙二醛（MDA）含量、热休克蛋白
70（HSP70）免疫组化染色及mRNA检测，肝组织石蜡切片HE
染色及电镜观察；结果：PC组ALT及MDA含量明显低于
I/R组（p＜0.01），肝组织损伤程度明显减轻；PC+L组在0—
3h阶段ALT和MDA含量与I/R组无显著区别（p＞0.05），而
在6—48h阶段则显著低于I/R组（p＜0.01）但仍高于PC组
（p＜0.05）。HSP70免疫组化染色：PC组、PC+L组3—48h
染色阳性率逐渐增多并显著高于I/R组（p＜0.01）；
第四军医大学98年级硕士学位论文
HSP70W表达逐渐增高，6一 12h 最高，其 PC组、PC＋L
组显著高于IR组一叩刀1人结论：缺血预处理对大鼠肝脏
缺血再灌注损伤具有明显保护作用，0—3h为早期保护效应，
可能为NO所触发或介导，6—48h为延迟保护效应（Late
Ischemic Preconditioning），HSP 70可能是导致延迟保护效应
的重要因素。
Objective: To study late preconditioning(PC) against ischemia/reperfusion(I/R) injury in rats liver. Methods 168 SD rats were divided into four groups: (1) S group: n=42,sham-operated control; (2)I/R group:n=42,Subjected to ischemic for 70-minute ischemia; (3) PC group: n=42,Two cycles of 5 min of ischemia followed by 5 min of reperfusion was performed before I/R;(4)PC+L group: n=42, L-NNA was administered before preconditioning then 70min ischemia. Followed by continuous reperfusion, serum ALT MDA NO NOS GSH GST and GSH-PX were examined in all groups during 0-48h; HSP 70 in the liver tissue were quantitatively analyzed and located by immunocytochemical technique. HSP 70 mRNA
were analyzed by PAGE Results Serum ALT and MDA in either I/R and PC+L group were markedly increased than in PC group (P<0.01) at any point after reperfusion.There is not significant difference between I/R group and P+L group during 0-3h(p>0.05) but during 6-48h(p<0.01). ALT and MDA were increased in PC+L vs PC group(p<0.05) and markedly decreased than I/R group during 6-48h(p<0.01). Expresstion of HSP 70 in PC and P+L group is gradually increased higher than in I/R group during 6-48h (P<0.01) ,so as HSP70 mRNA during l-12h.(p<0.01).Conc!usions: NO and HSP 70 might be participate in the protection against liver ischemia/reperfusion injury and NO might be protect liver in early preconditioning and HSP 70 might be associate with late preconditioning.
引文
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