摘要
目的观察Rho激酶抑制剂盐酸法舒地尔对日本血吸虫感染小鼠肝脏纤维化以及肝星状细胞(hepatic stel-late cells,HSCs)的影响。方法 30只雌性BALB/c小鼠随机均分为3组,分别为健康对照组、感染组和干预组,感染组和干预组小鼠经腹部皮肤感染日本血吸虫尾蚴(14±2)/只,感染后6周,干预组给予盐酸法舒地尔(10 mg/kg)腹腔注射,2次/d,连续7 d,健康对照组和感染组注射等体积生理盐水。末次注射12 h后剖杀小鼠,分别取健康对照组和感染组小鼠肝脏固定、切片,苏木素-伊红(HE)染色或天狼星红染色后镜下观察。检测3组小鼠肝脏羟脯氨酸(hydrox-yproline,Hyp)含量,以及α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原α1链(typeⅠcollagenα1,Col1α1)和上皮细胞转化序列2(epithelial cell transforming sequence 2,Ect2)的mRNA水平。采用原位灌注密度梯度离心法分离肝星状细胞,检测α-SMA、Col1α1和Ect2的mRNA水平。结果感染组小鼠肝内汇管区和虫卵肉芽肿周围炎症细胞浸润,胶原纤维增生。健康对照组、感染组和干预组每克肝湿重羟脯氨酸含量分别为(279.7±21.2)μg、(528.0±14.9)μg和(355.4±22.6)μg,干预组肝脏羟脯氨酸含量显著低于感染组(P<0.01)。干预组肝脏和肝星状细胞的α-SMA、Col1α1和Ect2的mRNA水平均显著低于感染组(均P<0.05)。结论盐酸法舒地尔对日本血吸虫感染小鼠肝纤维化有一定抑制作用。
Objective To investigate the anti-fibrotic effect of fasudil hydrochloride on Schistosoma japonicum-infected mice,and the effect of fasudil hydrochloride on hepatic stellate cells（HSCs）.Methods Thirty female BALB/c mice were randomly divided into 3 groups viz.normal control group（NC group）,infection group,and experiment group.Mice in both infection group and experiment group were infected with（14±2） cercariae of S.japonicum.At 6 weeks post infection,mice in experiment group were intraperitoneally injected with fasudil hydrochloride（10 mg/kg） twice a day for 7 d,while mice in NC group and infection group received the same volume of physiological saline.All mice were sacrificed 12 h after the last injection.Livers from NC group and infection group were used to prepare tissue sections for hematoxylin and eosin（HE） staining,or sirius red staining,and observed under light microscope.Livers from all three groups were used to detect content of hydroxyproline（Hyp） and the mRNA expressions of α-smooth muscle actin（α-SMA）,type Ⅰ collagen α1（Col1α1） and epithelial cell transforming sequence 2（Ect2）.HSCs from mice in all three groups were isolated to detect the mRNA levels of α-SMA,Col1α1,and Ect2,respectively.Results Pathological sections showed that in livers from mice in infection group,inflammatory cells infiltrated and collagenous fibre proliferated around portal areas and egg granulomas.The content of Hyp in liver from mice of NC group,infection group,and experiment group was（279.7±21.2） μg,（528.0±15.0） μg,and（355.4±22.6） μg,respectively.The content of Hyp in livers from mice of experiment group was significantly reduced compared to infection group（P0.01）.The mRNA expression of α-SMA,Col1α1 and Ect2 in livers and HSCs from mice in experiment group were significantly down-regulated compared to infection group（P0.05）.Conclusion Fasudil hydrochloride can depress hepatofibrosis in Schistosoma japonicum-infected mice.
出处
《中国寄生虫学与寄生虫病杂志》
CAS
CSCD
北大核心
2011年第3期183-188,共6页
Chinese Journal of Parasitology and Parasitic Diseases
基金
国家重点基础研究发展计划(973计划)(No.2007CB513102)~~
