不同+Gz重复持续暴露对大鼠肝脏组织损伤及GRP78的表达影响

The damage of liver cells and the expression of GRP78 in rats liver tissue after repeated and sustained exposure to different+Gz

目的探讨不同正加速度(+Gz)暴露下大鼠肝脏损伤及葡萄糖调节蛋白78(GRP78/Bip)在肝脏组织内分布和表达的变化。方法将SD大鼠24只,随机分为对照、+6Gz、+9Gz和+12Gz组,每组6只,峰值作用时间3 min,加速度增长率0.5 G/s,间隔30 min,重复间断连续5次。HE染色观察肝组织,并测定血浆天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT),用免疫组化法和Western blot测定肝脏组织中GRP78的表达。结果与对照组相比,+9Gz组、+12Gz组转氨酶水平均显著升高;且在ALT水平上,+12Gz组高于+9Gz组(P<0.05);HE染色显示正加速度组肝细胞排列紊乱,形态不规则,细胞间隙不清晰,空泡样改变,且随G值增长而加重。与对照组相比,GRP78/Bip表达分布主要集中在细胞胞质内;各实验组的GRP78表达均显著升高(P<0.05)。且+12Gz组明显高于+6Gz组和对照组(P<0.05),肝脏组织中GRP78/Bip蛋白表达水平随G值升高而升高;+12Gz组和+9Gz组都高于+6Gz组和对照组(P<0.05)。结论 GRP78/Bip的表达可能在加速度引起的肝脏应激反应有着正相关的作用。

Objective To observe the damage of liver cells and to investigate the distribution and expression of glucose-regulated protein 78( Glucose regulated protein78,GRP78 / Bip) in liver tissue under the positive acceleration( + Gz) exposure. Methods Totally 24 wistar rats were randomly assigned to four groups: blank control,+ 6Gz,+ 9Gz and + 12 Gz. Each rat was clamped to the centrifuge arm,prone position,with the head of the rat facing the axis of the centrifuge for + Gz orientation. The onset rate was + 0. 5 Gz / s,which was used trapezoidal acceleration curve effect and controlled by computer. Blank control group rats were placed on the arm of centrifuge and underwent a process similar to that described above,but they were not exposed to acceleration. + 6Gz group,+ 9Gz group and + 12 Gz group were subjected at peak time 3 min in animal centrifuge,acceleration rate 0. 5 G / s,five times withinterval 30 min between times. In addition,liver tissue of rats were respectively observed by H. E. staining. Mean while,plasma aspartate aminotransferase( AST) and alanine aminotransferase( ALT) were tested determine the damage of liver function. Results + Gz acceleration stress injury increased serum AST and ALT level. Compared with the stress control,+ 9Gz group and + 12 Gz group significantly increased in plasma ALT and AST as compared with control group( P < 0. 05). + 12 Gz stress induced the highest level in these groups. The level of ALT in + 2Gz group was higher than that in + 6Gz group( P < 0. 05). HE staining showed derangement of liver cells,irregular shape,the cell gap is not clear,vacuolar changes in + Gz groups,and with the increase of G value. Compared with the control group,the expression of GRP78 / Bip was focused in the cytoplasm; the expression of GRP78 in the experimental group is higher than that in the control group( P < 0. 05). + 12 Gz group was significantly higher than+ 6Gz group and the control group( P < 0. 05). The expression of GRP78 / Bip in liver tissue increased with the increasing of G value levels; the expression level of GRP78 / Bip in + 12 Gz and + 9Gz groups were higher than that in + 6Gz and control group( P < 0. 05). Conclusions There is positively related expression of GRP78 / Bip,which was associated with exposure of increasing G values.