神经生长因子对PM_(2.5)所致气道神经源性炎症影响的研究

Effect of nerve growth factor on airway neurogenic inflammation induced by PM_(2.5)

目的研究神经生长因子(nerve growth factor,NGF)调控PM_(2.5)所致大鼠气道神经源性炎症的机制。方法将40只SD大鼠随机分为5组:生理盐水对照组、PM_(2.5)组、IgG组、磷酸盐缓冲液(phosphate buffer saline,PBS)组、抗NGF组,每组8只。PM_(2.5)组以大鼠气道滴注PM_(2.5),盐水对照组以生理盐水代替PM_(2.5)。其他三组染毒前分别腹腔注射NGF抗体、IgG和PBS。通过观察大鼠血清中速激肽水平和各组肺组织病理变化确定模型的建立,检测血清中速激肽、NGF、肺组织、背根神经节中P物质(substance P,SP)表达。结果抗NGF组血清速激肽、NGF值低于PM_(2.5)组(P<0.05);PM_(2.5)组肺组织炎症细胞浸润明显,抗NGF组肺组织少量炎性浸润。各组大鼠肺组织中SP表达差异无统计学意义(P>0.05);抗NGF组背根神经节中SP表达低于PM_(2.5)组(P<0.05);抗NGF组肺组织及背根神经节中NGF表达低于PM_(2.5)组(P<0.05)。结论 NGF抗体可通过抑制血清及背根神经节中速激肽的表达减轻PM_(2.5)所致大鼠气道神经源性炎症。

Objective To explore the mechanism of nerve growth factor（NGF）regulating neurogenic inflammation of airway induced by PM2.5 in rats.Methods 40 SD rats were randomly divided into 5 groups：saline control group,PM2.5 group,IgG group,PBS group and anti-NGF group with 8 rats in each group.Rats in PM2.5 group were inoculated with PM2.5 suspended in saline through trachea,and rats in saline control group were given only saline.Rats in anti-NGF group were injected intraperitoneally with NGF antibody 3 hours before the exposure to PM2.5,and rats in IgG group and PBS group were treated with IgG and PBS instead of NGF antibody as the pretreatment control.A model was established by observing the pathological changes of lung tissue and measuring serum level of neurokinin by using ELISA method.Immunohistochemistry method was used to determine the expression of substance P（SP）in lung tissue and dorsal root ganglion.ResultsThe serum levels of neurokinin and NGF were lower in rats in anti-NGF group than those in PM2.5 group,the difference was statistically significant（P〈0.05）.Lung tissue pathological analysis showed that the inflammatory cell infiltration was more obvious in the lung tissue in PM2.5 group compared with rats in anti-NGF group.The expression of SP was lower in dorsal root ganglion of rats in anti-NGF group than rats in PM2.5 group（P〈0.05）,meanwhile,the expression of NGF in lung tissue as well as in dorsal root ganglion of rats in anti-NGF group was also lower compared rats in PM2.5 group（P〈0.05）.However,there were no significant differences of SP expression in lung tissue of rats in each experimental group（P〉0.05）.Conclusions Anti-NGF antibody may alleviate the neurogenic inflammation of airway induced by PM in rats by inhibiting the expression of neurokinin in dorsal root ganglia and reducing the serum level of neurokinin.