丝氨酸蛋白酶Omi/HtrA2的表达与大鼠肝功能衰老的关系

Relationship of serine protease Omi/HtrA2 expression with aging of liver function in rats

摘要:

目的 观察促凋亡蛋白丝氨酸蛋白酶Omi/HtrA2在衰老大鼠心、肾、肝、肺和脾中的表达情况，研究大鼠肝中Omi/HtrA2的表达与肝功能衰老程度的相关性。方法 选用3月龄、9月龄和22月龄雄性SD大鼠；多普勒超声方法检测动物心功能；血清生化方法检测动物的肝功能；免疫组化方法比较Omi/HtrA2在心、肝、肺、肾、脾中的表达情况；Western免疫印迹方法检测动物肝中Omi/HtrA2表达情况。结果 （1）在心、肾、肝和肺中，Omi/HtrA2表达量都很高，且蛋白的表达位置有一定的细胞特异性；与壮年组相比，衰老组大鼠的肝中Omi/HtrA2的表达量显著下降（P＜0.05），而在心、肾、肺组织中Omi/HtrA2的表达量也有下降的趋势，但差异无统计学意义（P＞0.05）；（2）与壮年组相比，衰老组动物肝功能指标：天冬氨酸氨基转移酶（AST）、血清铁（SI）、白蛋白（ALB）、白蛋白与球蛋白比值（A/G）都发生显著改变（P＜0.05）；衰老组动物的心功能指标：左室短轴缩短率（FS）和左室射血分数（LVEF）都有下降趋势，但差异无统计学意义（P＞0.05）；（3）与壮年组相比，中年组和衰老组大鼠的肝中Omi/HtrA2的表达量显著下降（P＜0.05），随着年龄增加肝功能逐渐降低，Omi/HtrA2的表达量与ALB和A/G呈显著正相关（P＜0.05）。结论 大鼠肝中Omi/HtrA2的表达量与肝功能呈正相关。

Abstract:

Objective To investigate the expression of proapoptotic serine protease, Omi/HtrA2, in the heart, kidneys, liver, lungs and spleen of rats at different ages and to explore the correlation between its expression and the aging of liver function. Methods Male SD rats at the age of 3, 9 or 22 months were employed in the study. Their heart function was evaluated by echocardiography, and liver function was tested by automatic biochemical analysis. The expression level and location of Omi/HtrA2 in the above mentioned organs were determined by immunohistochemical staining. The expression of Omi/HtrA2 in the liver was detected by Western blotting. Results (1) Omi/HtrA2 Was highly expressed in the heart, kidneys, liver and lungs of rats from different age groups, and mainly in certain types of cells in different organs. Compared with the young group, its expression was markedly decreased in the liver of rats from aged groups (P＜0.05). But no significant difference was seen in the other organs between the young and aged groups though with a trend of descending (P＞0.05). (2) There were significant differences in the liver function indices, such as the serum levels of aspartate aminotransferase (AST), serum iron (SI), albumin (ALB), and ratio of albumin to globulin (A/G) between the young and aged rats (P＜0.05). The cardiac function indicators, fractional shortening (FS) and left ventricular ejection fraction (LVEF) were in a trend of decreasing in the aged rats compared with the younger though without obvious difference (P＞0.05). (3) The expression level of Omi/HtrA2 was obviously reduced in the middle aged and aged rats than the young ones (P＜0.05). The liver function was also descended with aging. There was a positive correlation of the expression level of Omi/HtrA2 with the level of ALB and ratio of A/G (P＜0.05 ). Conclusion The liver expression of Omi/HtrA2t is positively correlated with liver function in rats.