一氧化氮及一氧化氮合酶抑制剂对小鼠血吸虫病肝纤维化程度的影响

Effect of nitric oxide and nitric oxide synthase inhibitor on liver fibrosis of mice infected with Schistosoma japonicum

目的研究一氧化氮(NO)对小鼠日本血吸虫病肝纤维化程度的影响。方法昆明小鼠经腹部皮肤感染日本血吸虫,于感染后第4周末治疗组和抑制剂组分别给予NO前体-L-精氨酸(L-Arg)及一氧化氮合酶(NOS)抑制剂-NG-左旋-硝基精氨酸甲基乙酯(L-NAME),于第10周末处死小鼠,取血,分离血清,剖取肝脏。应用病理组织学方法及生物化学方法,观察各组小鼠血吸虫病肝纤维化程度,同时测定血清NO、层粘连蛋白(LN)、透明质酸(HA)、谷-草转氨酶(AST)及谷-丙转氨酶(ALT)活性和肝组织羟脯氨酸(Hyp)含量。结果小鼠感染血吸虫后,感染组肝脏有明显的纤维化,血清中HA、LN、AST、ALT等指标显著升高,肝组织内Hyp含量也明显增加。与感染组相比:L-Arg高、中剂量组肝纤维化程度评分降低显著,低剂量组虽有减轻但无统计学意义,同时,L-Arg高、中剂量组血清LN、HA、AST、ALT的水平和肝组织Hyp的含量有所降低;低剂量组HA、LN、AST、ALT的水平虽然降低,但无统计学意义,Hyp水平降低明显;抑制剂组血清LN、HA、AST、ALT含量和肝组织Hyp的水平均明显升高。血清NO的水平随着精氨酸剂量的增加而显著增加,而精氨酸抑制剂组NO的水平降低明显。结论NO能明显降低血吸虫病肝纤维化的程度和减轻肝纤维化所造成的损伤作用。

To observe the effect of nitric oxide（NO） and nitric oxide synthase（NOS） inhibitor on the liver fibrosis induced by Schistosoma japonicum in mice, Kunming mice （KM） were infected with 25 cercariae of S. japonicum for each mouse through skin of abdomen. At the end of 4 weeks after infection , NO-precursor L-arginine （L-Arg） and NOS inhibitor L- NAME were given to the respective mice, and at end of 10 weeks after infection, mice were sacrificed and serum and liver tissue were taken for examinations. The degree of hepatic fibrosis induced by S. japonicum in various groups of mice was examined by histopathological and biochemical methods. Meanwhile, the contents of NO, laminin（LN）, hyaluronic acid （HA）, AST and ALT in serum and the hydroxyproline （Hyp） content in liver homogenates were determined accordingly. It was demonstrated that remarkable liver fibrosis and significant elevations of serum levels of HA, LN, AST ALT and the Hyp content in liver homogenates could be found in mice infected with S. japonicum. In comparison with the mice infected, the degree of liver fibrosis in mice receiving high and middle dosages of L-Arg was significantly reduced. However, although those of mice receiving low dosage still showed certain degree of reduction in liver fibrosis, but not statistical difference could be demonstrated. The reduction of the Hyp level was quite remarkable, and the levels of LN, HA, AST, ALT in serum and Hyp level in liver were significantly elevated in mice receiving L-NAME in comparison with those of mice infected. In addition, the content of Hyp was lower in liver of mice receiving L-Arg, but was higher in liver of mice receiving L-NAME than those of the infected mice. The level of NO in serum elevated significantly along with the increase of dosage of L-Arg, but it was significantly decreased in mice receiving L-NAME. It is concluded that NO can remarkably reduce the degree of hepatic fibrosis induced by S. japonicurn, thus lessening its damages.