CAJ | 학술논문

为探讨慢性束缚应激对大鼠脑内不同部位Fas／FasL系统表达的不同影响。将24只雄性sD大鼠随机分为束缚应激组、装置对照组和正常对照组（n=8）。分别对三组大鼠给予相应的干预14天，用Western-blotting方法测定应激后大鼠大脑前脑皮质、内嗅皮质以及海马区域Fas、FasL蛋白含量。结果表明，应激后各脑区三组大鼠Fas含量差异具有统计学意义（P〈0．01），束缚应激组明显高于正常对照组或装置对照组（p〈0．01）。在海马区域，三组大鼠FasL含量差异具有统计学意义（P〈0．01），束缚应激组大鼠FasL蛋白水平显著高于正常对照组或装置对照组（p〈0．01）。三组大鼠自身大脑前脑皮质、内嗅皮质以及海马Fas含量的差异比较均无统计学意义（P〉0．05）。束缚应激组大鼠海马的FasL含量高于前脑皮质和内嗅皮质（P〈0．05）；正常对照组或装置对照组自身不同脑区间FasL含量的变化无统计学意义。提示慢性束缚应激能诱导大鼠脑内Fas／FasL系统表达水平的改变。对不同的脑区，其影响程度明显不同。
위탐토만성속박응격대대서뇌내불동부위Fas／FasL계통표체적불동영향。장24지웅성sD대서수궤분위속박응격조、장치대조조화정상대조조（n=8）。분별대삼조대서급여상응적간예14천，용Western-blotting방법측정응격후대서대뇌전뇌피질、내후피질이급해마구역Fas、FasL단백함량。결과표명，응격후각뇌구삼조대서Fas함량차이구유통계학의의（P〈0．01），속박응격조명현고우정상대조조혹장치대조조（p〈0．01）。재해마구역，삼조대서FasL함량차이구유통계학의의（P〈0．01），속박응격조대서FasL단백수평현저고우정상대조조혹장치대조조（p〈0．01）。삼조대서자신대뇌전뇌피질、내후피질이급해마Fas함량적차이비교균무통계학의의（P〉0．05）。속박응격조대서해마적FasL함량고우전뇌피질화내후피질（P〈0．05）；정상대조조혹장치대조조자신불동뇌구간FasL함량적변화무통계학의의。제시만성속박응격능유도대서뇌내Fas／FasL계통표체수평적개변。대불동적뇌구，기영향정도명현불동。
there exists a substantial body of evidence suggesting that chronic stress can increase susceptibility to diseases such as depression and posttraumatie stress disorder. Chronic stress induces neuronal atrophy and death in the cortex as well as in the hippoeampus. Proto - oncogene protein kinase B （PKB）, also known as Akt, plays a central role in a signaling pathway whose various components have been linked to cellular survival. In recent years, Akt as well as one of its downstream targets Forkhead transcription factors （forkhead homologne in rhabdomyosarcoma, （FKHR）） and the Fas/FasL system have emerged as cardinal pathways underlying cellular survival and opposing apoptosis in neurons. In our previous experiments, we observed that repeated immobilization stress exposure can change the levels of phosphorylation of Akt and FKHRL1 in the rat hippoeampus. However, the activation of the Fas/FasL system following chronic stress in the brain remains poorly defined. We hypothesized that repeated immobilization stress exposure may change the levels of the Fas/FasL system in the brains of rats. The purpose of the present study was to detect the effects of chronic immobilization stress on the expression of Fas/FasL in the prefrontal cortex, entorhinal cortex, and hippocampus in rats. Twenty four male Sprague - Dawley rats （280 ± 20g） were purchased from Shanghai Laboratory Animal Center, Chinese Academy Sciences, and they were used for all experiments. These rats were randomly divided into three groups - the immobilization stressed group, apparatus control group, and control group. Each group comprised eight rats. The rats were housed in groups of four, under standard laboratory conditions in temperature - controlled rooms （24℃）, and maintained under a 12 - h fight/dark cycle （lights on at 0800 hours） with food pellets and water available ad libitum. Rats from the immobilization stressed group were immobilized by fixing a board on their backs for an hour each day for 14 consecutive days. The apparatus controls were placed in a novel environment for an hour per day for 14 consecutive days. The controls were free of stress. At the end of the experimental period, the rats were decapitated and their prefrontal cortex, entorhinal cortex, and hippocampi were rapidly removed and maintained at - 80℃ until analysis. The protein levels of Fas and FasL were determined by Western blotting. The intensities of the bands corresponding to the protein of interest were quantified using scanning densitometry and compared using one - way ANOVA. The adrenal gland and thymus gland indices were also calculated on the day following the 14 - day - stress modeling, Organ index = wet weight/weight of rat × 100. The statistical significance was determined at p 〈 0.05. A total of 24 rats were considered in the analysis of the results. The body weight gain of the stressed group was significantly lower than that of the control group and the apparatus control group. A significant change was observed in the organ indices of the stressed groups as compared to the control group. The Fas and FasL levels of the hippocampus revealed a significant difference amongthree groups （F = 26.9,p 〈 0.001;F = 4029,p 〈 0.01, respectively）. The Fas and FasL levels were significantly increased in the immobilization stressed group than in the control group （p 〈 0.01）. The Fas levels of the prefrontal cortex and entorhinal cortex in the immobilization stressed group were significantly increased than those in the control group （p 〈 0.01）. In contrast, the FasL levels of the prefrontal cortex and entorhinal cortex did not reveal a significant deference between the immobilization stressed group and control group. The results suggested that chronic immobilization stress can induce a more significant increase in both the Fas and FasL levels in the hippocampus. Changing the expression of Fas/FasL may be an effective biological predictor for the change of structure or function of hippocampus induced by chronic stress in rats.