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

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

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7d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、7d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、7d，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。

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 LiCI 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 LiCI provides neuroprotection against ICH by inhibiting neural cell apoptosis and reducing inflammatory response through down-regulation of NF-κB expression.