宫内炎症对仔鼠脑组织TLR4表达的影响

The effect of intrauterine inflammation on the expression of TLR4 in immature rat brain

目的:探讨胎鼠及新生大鼠脑中TLR4及细胞因子TNF-α在宫内感染后脑损伤中的作用。方法:取孕龄17、18天(足月为22.5天)的SD大鼠,每次350μg/kg、连续2天腹腔注射,构建宫内感染大鼠模型(LPS组);对照组孕鼠腹腔注射同剂量的生理盐水(NS组)。观察胎盘和脑组织的病理改变。分别留取孕20、21天及生后1、3、7、14天(P1、P3、P7、P14)的新生大鼠脑标本,检测细胞因子TNF-α、TLR4的表达情况。结果:LPS组新生大鼠脑组织HE染色可见细胞水肿,组织疏松,细胞数减少。蛋白表达结果显示LPS组TLR4明显升高,较NS组差异有统计学意义,F=71.148,P=0.001;LPS组TNF-α较NS组差异有统计学意义,F=16.863,P=0.015。LPS组TLR4、TNF-αmRNA在G20、G21、P1、P3、P7的表达比NS组明显升高,差异有统计学意义(P<0.05),而在P14两组差异无统计学意义(P>0.05)。结论:宫内LPS感染后TLR4信号途径被激活,诱导炎性因子大量释放,最终导致脑损伤的发生。

Objective：To investigate the relationship between neonatal brain damage and inflammatory response through identifying the expression of TLR4 and TNF-α in fetal and neonatal brain.Methods：In the present study,Sprague-Dawley （SD） rats （n=20） at day 17 and 18 of gestation underwent treatment for two days.The intrauterine infection rat model （LPS-treated group） was set up through intraperitoneal LPS administration （350 μg/kg）,while the control group was administrated of the same volume of pyrogen-free saline （NS-treated group）.The placenta and pathological changes of brain tissue were observed Brain tissues were collected from the fetal rat at pregnant day 20,21 and neonatal rat at postnatal day 1 （P1）,P3,P7 and P14.Expressions of TLR4 and TNF-α were detected.Results：Brain hematoxylin-eosin staining showed cellular edema,tissue raritas and cell population decreased in the LPS-treated group.Protein expression showed TLR4 in LPS-treated group was significantly increased compared to that of the control group （F=71.148,P=0.001）.TNF-α in the LPS-treated group was significantly increased than that of the control group （F=16.863,P=0.015）.The expression of TLR4,TNF-α mRNA in LPS-treated group were significantly increased compared to that of the control group in G20,G21,P1,P3,P7 rat brain （P 0.05）.There was no significant difference on TLR4 and TNF-α mRNA levels between the LPS-treated group and the NS-treated group at the P14 neonatal rat brain （P 0.05）.Conclusion：Intrauterine LPS exposure can induce TLR4 signal pathway activa-tion and induce the releasing of inflammatory factor greatly,and eventually result in brain damage.