慢性应激对大鼠行为和免疫细胞热休克蛋白70表达的影响

Effects of Chronic Stress on Behavior and Heat Shock Protein 70 Expression in Immune Cells

目的:研究慢性不确定应激对大鼠急性整体热水浴后外周血和脾脏免疫细胞热休克蛋白70(Heat shock protein 70,HSP70)表达的影响。方法:随机将大鼠分成慢性应激组和控制组(每组14只)。通过4周的慢性不确定性应激诱发实验组大鼠明显的抑郁行为,此期间控制组大鼠正常饲养。随后给予大鼠42度整体热水浴刺激,维持直肠温度41°25min。热刺激后6h,采用流式细胞仪测定大鼠外周血和脾脏免疫细胞HSP70水平。结果:与控制组大鼠相比,慢性应激大鼠在急性热刺激后HSP70合成明显减少。控制组大鼠的所有被检测的免疫细胞热应激后HSP70合成均明显增加。相反,慢性应激大鼠仅在外周血的单核细胞和粒细胞检测到HSP70合成增加,同时升高的水平明显低于控制组大鼠。结论:慢性应激降低大鼠免疫细胞HSP70的热诱导反应,提示HSP70保护性作用减弱可能参与了慢性应激损害免疫细胞功能的生物学过程。

Chronic stress can suppress organisms＇ resistance to adverse stimuli in the environment. The stress responses occur at both the system and single-cell levels. Although many studies have investigated the neuroendocrine mechanisms underlying the effects of stress on health, the characteristics of cellular stress response are still poorly understood. One manner in which cells resist damage and/or death induced by stress is to synthesize a highly conserved set of intracellular proteins, termed heat shock protein （HSP）. In particular, the 70-kDa HSP （HSP70） is essential for cellular recovery after stress as well as survival and maintenance of normal cellular function. It has been demonstrated that the expression of high levels of HSP70 is associated with an increased resistance of cells to challenges that would otherwise lead to cell injury and/or death. Therefore, the intensity of an HSP70 response to stress is an important biomarker of how the cell tolerates stress damage. This study aimed to determine whether prior chronic stress inhibited the synthesis of HSP70 in immune cells in the peripheral blood and spleen of rats exposed to an acute hot water bath. Twenty-eight rats were randomly divided into 2 groups with 14 rats in each group： the control group （C） and the chronic stress group （CS）. CS rats were exposed to chronic unpredictable stress for 4 weeks to induce depressive-like behavior. The controls were stress-free. Thereafter, 8 rats in each group were exposed to acute heat stress （C-heat shock and CS-heat shock） to induce whole-body hyperthermia （maintaining the core temperature at 41~C for 25 minutes ）. The other rats remained undisturbed in their home cages （C-no heat shock and CS-no heat shock）. All rats were decapitated 6 hours after the completion of the treatments. The blood and spleen were collected and the level of HSP70 expression in the leukocytes was measured using flow cvtometrv. It was found that CS rats showed a decreased cellular HSP70 expression following the heat treatment, while a significant increase in the synthesis of HSP70 was observed in all types of immune cells from C rats. However, in CS rats, such HSP70 changes were only detected in the monocytes and granulocytes. Further, the increasing degree of heat- induced cellular HSP70 expression in CS rats was less pronounced than that observed in C rats. These results demonstrated that chronic stress decreased heat-induced HSP70 response in immune cells. Further, they suggested that the deficit of HSP70 might be involved in the suppressive modulation of the immune function induced by chronic stress.