重组人干扰素α1b与炎琥宁和喜炎平抗呼吸道合胞病毒感染的对照研究

Comparison of the effects of recombinant human interferon α1b, Yanhuning and Xiyanping against respiratory syncytial virus infection

目的比较重组人干扰素α1b与炎琥宁、喜炎平对呼吸道合胞病毒(RSV)感染小鼠的抗病毒与调节T淋巴细胞亚群的作用。方法将BALB/c小鼠随机分为8组,建立RSV感染小鼠模型,分别给予重组人干扰素α1b腹腔注射(12.5μg/kg)、重组人干扰素α1b雾化吸入(12.5μg与25.0μg)、利巴韦林腹腔注射(123.3 mg/kg)、喜炎平腹腔注射(61.65 mg/kg)、炎琥宁腹腔注射(61.65 mg/kg)连续5 d的干预治疗,同时设RSV感染阳性组和阴性对照组。于第6天摘眼球取血,流式细胞术检测小鼠外周血CD3+CD4+、CD3+CD8+水平;无菌剖取肺组织,光镜、透射电镜下观察小鼠肺组织病理学改变;荧光定量PCR法检测小鼠肺组织RSV载量。结果成功建立RSV感染小鼠模型。光镜及透射电镜下观察RSV感染阳性组小鼠肺组织炎性损伤明显,重组人干扰素α1b与炎琥宁、喜炎平干预治疗后,小鼠肺组织炎性损伤有不同程度恢复,RSV载量显著下降,其中重组人干扰素α1b 25.0μg雾化吸入组小鼠肺组织炎性损伤程度最轻,RSV载量最低,喜炎平、炎琥宁腹腔注射组次之,各组间比较差异均有统计学意义(P<0.05)。与RSV感染阳性组比较,重组人干扰素α1b与炎琥宁、喜炎平干预各组小鼠外周血CD3+CD8+水平升高,CD3+CD4+与CD3+CD4+/CD3+CD8+水平降低,差异均具有统计学意义(P<0.05);其中重组人干扰素α1b 25.0μg雾化吸入组,调节T淋巴细胞亚群作用显著,喜炎平、炎琥宁腹腔注射组次之,差异均有统计学意义(P<0.05),喜炎平与炎琥宁两组比较差异无统计学意义(P>0.05)。结论重组人干扰素α1b与炎琥宁、喜炎平均有抗RSV及调节T淋巴细胞亚群作用,其中重组人干扰素α1b 25.0μg雾化吸入组最为显著。

Objective To investigate and compare the effects of recombinant human interferon α1b, Yanhuning and Xiyanping on antagonizing respiratory syncytial virus （RSV） and regulating T lymphocyte subsets in RSV infected mice. Methods BALB/c mice were divided into eight groups randomly and the RSV infected-mouse model was established. Groups were given inhaled recombinant human interferon α1b of 12.5 μg and 25.0 μg, intraperitoneal injection of recombinant human interferon α1b （12.5 μg/kg）, ribavirin （123.3 mg/kg）, Xiyanping （61.65 mg/kg） and Yanhuning （61.65 mg/kg）, respectively in five consecutive days. RSV infection positive and negative control groups were also set. The eyeball blood of mice was taken in the sixth day and the levels of CD3＋CD4＋, CD3＋CD8＋ in peripheral blood were tested by flow cytometry. The lung histopathology of sterile sectional lung tissue was observed by light microscopy and transmission electron microscope, and the fluorescence quantitative PCR was used to test the RSV load. Results The mouse model of RSV infection was successfully established. Significant inflammatory injury in RSV-infection positive mice’s lungs was observed under light microscope and transmission electron microscopy. After treatments of recombinant human interferon α1b, Yanhuning or Xiyanping, the mice lung tissue showed recovery of inflammation with different degrees and RSV load significantly decreased. Wherein, the group of inhaled recombinant human interferon α1b 25.0 μg had the lightest degree of damage and the lowest RSV load. Intraperitoneal injected Xiyanping and Yanhuning groups were less effective. There were statistically significant differences between each group （P 0.05）. Conclusions Recombinant human interferon α1b, Xiyanping and Yanhuning all played a role in anti-RSV effects and T lymphocyte subsets regulation. Among these treatments, the group with inhaled recombinant human interferon α1b 25.0 μg had the most significant effect.