Hong Ming-yan, Cui Jian-zhong, Li Ran, Tian Yan-xia, Wang Huan, Wang Hai-tao, Gao Jun-ling
Department of Surgery, Hebei Medical University, Shijiazhuang 050017, China.
Zhonghua Wai Ke Za Zhi. 2012 Feb 1;50(2):166-70.
To study the effect and potential mechanism of expression of c-jun N-terminal kinase (JNK) signal pathway on neuron autophagy after diffuse brain injury (DBI).
Male Sprague Dawley rats (n = 216) were randomly divided into four groups: DBI group (n = 54), SP600125 intervene group (n = 54), DMSO group (n = 54) and sham operation group (n = 54). DBI rat model was established according to the description of Marmarou DBI. At different time points (1, 6, 12, 24, 48 and 72 h) after operation, the histopathologic changes of neurons in cortex were observed by HE staining method; The expression of p-JNK, p-P53, DRAM and Beclin-1 were detected by Western blot and immunohistochemistry.
The results showed that under light microscope degenerated and necrotic neurons were observed to be scattered in cortex at 6 h after operation in DBI group, but these changes were low in SP600125 intervene group. Compared with SP600125 intervene group, the expression of p-JNK in DBI group were enhanced obviously at 6, 12 and 24 h (F = 17.902, P < 0.05); the expression of p-P53 in DBI group were enhanced obviously at 12, 24, 48 and 72 h (F = 7.107, P < 0.05); the expression of DRAM in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 15.455, P < 0.05); the expression of Beclin-1 in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 11.517, P < 0.05). Compared with DBI group, the expression of p-JNK, p-P53, DRAM and Beclin-1 in DMSO group were similar at 1, 6, 12, 24, 48 and 72 h (F = 1.509, P > 0.05).
The present results indicate that SP600125 can dramatically improve trauma brain injury from autophagy after DBI and the molecular mechanism is related to the modulation of JNK signal pathway following DBI, while it measures the neuron autophagy by means of intervening JNK signal pathway.
研究c-Jun氨基末端激酶（JNK）信号通路表达对弥漫性脑损伤（DBI）后神经元自噬的影响及潜在机制。
将216只雄性Sprague Dawley大鼠随机分为四组：DBI组（n = 54）、SP600125干预组（n = 54）、二甲基亚砜（DMSO）组（n = 54）和假手术组（n = 54）。根据Marmarou DBI的描述建立DBI大鼠模型。术后不同时间点（1、6、12、24、48和72小时），采用苏木精-伊红（HE）染色法观察皮质神经元的组织病理学变化；采用蛋白质免疫印迹法和免疫组织化学法检测p-JNK、p-P53、损伤调节自噬激活因子（DRAM）和Beclin-1的表达。
结果显示，光镜下DBI组术后6小时可见皮质散在变性坏死神经元，但SP600125干预组这些变化较少。与SP600125干预组相比，DBI组在6、12和24小时时p-JNK表达明显增强（F = 17.902，P < 0.05）；DBI组在12、24、48和72小时时p-P53表达明显增强（F = 7.107，P < 0.05）；DBI组在6、12、24、48和72小时时DRAM表达明显增强（F = 15.455，P < 0.05）；DBI组在6、12、24、48和72小时时Beclin-1表达明显增强（F = 11.517，P < 0.05）。与DBI组相比，DMSO组在1、6、12、24、48和72小时时p-JNK、p-P53、DRAM和Beclin-1的表达相似（F = 1.509，P > 0.05）。
目前的结果表明，SP600125可显著改善DBI后自噬引起的创伤性脑损伤，其分子机制与DBI后JNK信号通路的调节有关，同时它通过干预JNK信号通路来调控神经元自噬。
