探讨神经营养因子(neurotrophin, NT)-3在肺炎链球菌性脑膜炎脑组织及抗生素治疗后的表达变化特点。

将3周龄SD大鼠46只(雌、雄不限，昆明医学院动物研究所提供)，采用(0.15～0.30)mL/100 g 10%水合氯醛腹腔注射麻醉后，建立肺炎链球菌性脑膜炎脑损伤模型(n＝34)。建模成功后，根据是否接受进一步治疗，随机分成感染组(n＝20)、治疗组(n＝14)。其余纳入正常对照组(n＝12)。各组间大鼠的平均体重和鼠龄比较，差异无显著意义(P>0.05)。①46只大鼠均行脑池穿刺，感染组和治疗组接种50 μL肺炎链球菌混悬液，正常对照组接种50 μL生理盐水。观察神经营养因子-3在脑组织中的表达。经自然病程，感染组大鼠分别于接种后24 h和第5天处死(24 h感染组，n＝8; 5 d感染组，n＝12)。②将治疗组分为抗生素治疗组(n＝8)和抗生素对照组(n＝6)，前者给予头孢曲松皮下注射治疗3 d后，与正常对照组神经营养因子-3在脑组织中的表达进行比较。后者不做任何处理。③正常对照组于接种生理盐水后24 h(24 h正常对照组，n＝6)和5 d(5 d正常对照组，n＝6)分别处死。

在脑皮质和海马中，24 h感染组，与正常对照组比较，神经营养因子-3明显下降(P<0.01)，第5天回升(5 d感染组)，但仍未达到正常对照组水平(P<0.05)。抗生素治疗组神经营养因子-3蛋白表达水平低于抗生素对照组，差异有显著意义(P<0.05)，与5 d感染组比较，差异无显著意义(P>0.05)；抗生素对照组与5 d正常对照组神经营养因子-3蛋白的表达比较，差异无显著意义(P>0.05)。

大鼠罹患肺炎链球菌性脑膜炎时，神经营养因子-3在脑组织中的表达下降。在肺炎链球菌性脑膜炎急性脑损伤中，神经营养因子-3对神经的保护支持作用可能减弱。在肺炎链球菌脑膜炎中，抗生素治疗后，神经营养因子-3在脑组织中的表达仍处于较低水平，在肺炎链球菌性脑膜炎脑损伤中，神经营养因子-3的内源性神经保护作用可能仍不能恢复。

To investigate the expression of neurotrophin-3 (NT-3) expression in brain injury after antibiotic therapy of meningitis induced by Streptococcus pneumoniae.

A total of 46 SD rats, 3-week old, either male or female, received 10% chloral hydrate at the concentration (0.15-0.30)mL/100 g by intraperitoneal injection. Among them, 34 rats were established the brain damage in pneumococcal meningitis model successfully, which were divided into infection group (n=20) and treatment group (n=14). The rest rats were included into control group(n=12). There was no significant difference of average weight and age among three group (P>0.05). ①All of them underwent cisternal puncture. Infection group and treatment group received an equivalent volume of a Streptococcus pneumoniae suspension and control group received sterile saline as a placebo. The expression of neurotrophin-3 in the brain were observed (×400). The rats were sacrificed at 24 h or 5 d post-infection and cortex were harvested (24 h infection group and 5 d infection group). The expressions of neurotrophin-3 protein were detected by immunohistochemical staining methods in cerebral cortex and hippocampus. ② Infection group were further divided into two sub-groups. Antibiotic treatment group (n=8) received subcutaneous injection of ceftriaxone treatment for 3 days, and antibiotic control group (n=6) received no treatment. ③ Control group were sacrificed immediately after 24 hours, 5 days after receiving saline (24 h control group and 5 d control group).

In cerebral cortex and hippocampus, the expression of neurotrophin-3 was declined obviously at 24 h infection group and then restored in 5 d infection group, compared to control group (P<0.01, P<0.05). The expression of neurotrophin-3 protein in antibiotic treatment group was lower than that of antibiotic control group (P<0.05).

The expression of neurotrophin-3 declined in the brain of rats after meningitis induced by Streptococcus pneumoniae. Neurotrophin-3 supporting role in the protection of the nerve may be reduced in Streptococcus pneumoniae meningitis acute brain injury. After administration with antibiotics, neurotrophin-3 expression still at low level and its endogenous neuroprotection may still not be restored.