法舒地尔对脑出血大鼠神经功能的影响

目的 探讨法舒地尔对脑出血大鼠神经功能的保护作用及机制。方法 将60只SD大鼠随机分为:假手术组、模型组、低剂量法舒地尔组（低剂量组）和高剂量法舒地尔组（高剂量组）；每组15只。通过注射自体脑内动脉血制作脑出血模型，假手术组只暴露硬脑膜，不注射动脉血。低剂量组腹腔注射1 mg/（kg·d）法舒地尔，高剂剂量组腹腔注射10 mg/（kg·d）法舒地尔。模型组和假手术组腹腔注射等体积生理盐水。药物干预4周后，使用Y-迷宫法评价大鼠学习记忆功能，记录大鼠错误反应次数；使用Longa法评价大鼠神经功能。干湿重法测定脑组织含水量，使用硝酸溶解法测定Na+、K+含量，TUNEL染色分析神经细胞凋亡率，免疫印迹法分析凋亡相关蛋白表达（Bax、Bcl-2和Caspase-3）。结果 相比假手术组，模型组大鼠逃离错误次数、Longa神经功能评分、脑组织含水量、脑组织Na+离子水平、神经细胞凋亡率、Caspase-3和Bax蛋白表达水平显著升高（P<0.01），脑组织K+离子水平、Bcl-2蛋白表达水平显著降低（P<0.01）。相比模型组，法舒地尔模型逆转大鼠脑出血后上述变化（P<0.01），而且高剂量法舒地尔明显优于低剂量法舒地尔（P<0.01）。结论 大鼠脑出血后，法舒地尔可以调节神经细胞Na+、K+离子平衡并减少脑组织水肿、抑制神经细胞凋亡，保护大鼠神经功能

Effects of fasudil on nerve function in rats after cerebral hemorrhage

Objective To explore the protective effect and the mechanism of fasudil on nerve function of rats after intracerebral hemorrhage (ICH). Methods Sixty rats were randomly divided into four groups, i.e., sham operation group, model group, low-dose fasudil group and high-dose fasudil group, with 15 rats in each group. The ICH model was made by injecting autologous intracerebral arterial blood. In the sham operation group, only the dura mater was exposed and no arterial blood was injected. The rats in low-dose and high-dose groups were intraperitoneally injected with 1 mg/(kg·d) and 10 mg/(kg·d) fasudil, respectively. The rats in model and sham operation groups were intraperitoneally injected with the same volume of normal saline. After 4 weeks of treatment: the Y-maze method was used to evaluate the learning and memory function of rats, and the number of wrong reactions in rats was recorded; the Longa method was used to evaluate the neurological function of rats; the water content of brain tissue was determined by dry and wet weight method; the Na+ and K+ contents were determined by nitric acid dissolution method; the apoptosis rate of nerve cells was analyzed by TUNEL staining, and the apoptosis-related protein expression (Bax, Bcl-2 and Caspase-3) was analyzed by western blotting. Results Compared with the sham operation group, the number of times of error escape, Longa nerve function score, brain tissue water content, brain tissue Na+ level, nerve cell apoptosis rate, and protein expression levels of Caspase-3 and Bax were significantly increased in the model group (P<0.01), but brain tissue K+ level and protein expression level of Bcl-2 were significantly reduced (P<0.01). The fasudil reversed the above changes after ICH in rats (P<0.01), and the high-dose fasudil was significantly better than the low-dose fasudil (P<0.01). Conclusion After ICH in rats, fasudil can adjust the balance of Na+ and K+ in nerve cells, reduce brain edema and nerve cell apoptosis, and protect rat nerve function