氯化锂预处理对脑出血后血肿周围神经细胞凋亡及核因子κB表达的抑制作用

目的 观察氯化锂预处理对大鼠脑出血后血肿周围神经细胞凋亡、炎症反应及核因子κB(NF-κB)表达的影响.方法 54只SD大鼠按随机数字表法分为假手术组、脑出血组和氯化锂预处理脑出血组,每组各18只.氯化锂预处理脑出血组手术前7 d起每天腹腔注射氯化锂(1mmol/kg).利用立体定向技术,将Ⅳ型胶原酶用微量进样器精确注入大鼠内囊诱导成脑出血模型.跟据术后处死动物的时间不同,各组再分别分为1、3、7 d三个亚组.分别采用TUNEL法、苏木素-伊红染色和免疫组织化学染色观察血肿周围神经细胞凋亡、炎症反应及NF-κB表达的情况.结果 在脑出血后1、3、7 d,与脑出血组(TUNEL阳性细胞数:18.32±3.75,33.24±6.37,20.49±4.87;NF-κB阳性细胞数:55.34±5.83,30.63±3.27,9.53±2.37)比较,氯化锂预处理脑出血组血肿周围区TUNEL阳性细胞数(15.84±3.12,10.88±4.75,5.83±4.39)明显减少,NF-κB阳性细胞数(29.27±3.37,16.36±3.64,7.64±2.31)明显降低,比较差异有统计学意义(P<0.05),炎症反应也明显减轻.结论 氯化锂预处理可能通过降低NF-κB的表达来减轻脑出血后的炎症反应,减少脑出血后血肿周围神经细胞凋亡,其对脑出血后脑损伤有神经保护作用.

Lithium chloride inhibits neural cell apoptosis and nuclear factor kappa B protein expression in rats with intracerebral hemorrhage

Objective To observe the effects of lithium chloride (LiCl) on neural cell apoptosis, inflammatory response and expression of nuclear factor kappa B (NF-κB) protein in rats with intracerebral hemorrhage (ICH). Methods Fifty-four male SD rats were randomized into sham-operated, ICH and LiCl treatment groups (n=18), and in the latter two groups, ICH was induced by injection of collagenase Ⅳ into the internal capsule, and phosphate buffer solution was injected in the sham-operated group. Seven days before ICH, the rats in LiCl group received intraperitoneal injection of 1 mmol/kg LiCl once daily till the rats were sacrificed. Brain tissue specimens were collected at 1, 3, and 7 d after ICH to observe neural cell apoptosis, inflammatory response and expression of NF-κB in rat brain using terminal dUTP nick end-labeling (TUNEL), HE staining and immunohistochemistry, respectively. Results Compared with the ICH model group, the rats in LiCl treatment group showed significantly reduced number of TUNEL-positive cells in the brain tissues around the hematoma at 1, 3, and 7 days after ICH (P<0.05). NF-κB protein expression was observed 1 day after ICH, which reached the peak level on day 3 and lowered 7 days after ICH. LiCl treatment significantly lowered the expression of NF-κB protein in comparison with that in ICH group (P<0.05) and obviously ameliorated the inflammatory responses in the brain tissues. Conclusion LiCl provides neuroprotection against ICH by inhibiting neural cell apoptosis and reducing inflammatory response through down-regulation of NF-κB expression.