柴石解毒颗粒对感染登革2型病毒的1型干扰素受体阻断小鼠疗效的研究

Study on efficiency of Chaishi Jiedu Granules on type 1 interferon receptor blocked mouse infected with dengue 2 virus

目的:验证柴石解毒颗粒的有效性及机制,尝试使用初步建立的抗体阻断1型干扰素受体C57BL/6小鼠模型进行药物效果评价。方法:将3周龄的C57BL/6小鼠在攻毒前1天进行2.5 mg的1型干扰素受体抗体的腹腔注射,随后进行4×10;PFU DENV-2 NGC株的攻毒,攻毒后第1天开始进行2次/d的灌胃给药、症状观察、血清中病毒滴度及肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平的测定,最后对感染小鼠脑、肝、肾、脾进行组织病理学分析。结果:中药组小鼠体内血清病毒滴度水平与模型组比较低且平缓,感染后6 d内处于1×10;copies/mL的数量级,没有出现突然上升的现象;与仅攻毒对照组、完全对照组比较,体质量增加虽受到了一定抑制,但较阳性药组显著增加(P<0.05)。同时,中药组血清中TNF-α、IL-6水平分别于感染后第4、6天显著低于模型组(P<0.05)。脑部和肾脏病理分析结果显示阳性药组病变最严重,其次为模型组,最轻微为中药组。结论:该方的应用,使得小鼠体内的血清中病毒滴度处于平缓状态,同时避免了炎症因子水平过激的情况。

Objective: To confirm the efficacy and mechanism of Chaishi Jiedu Granules and try to use the preliminary established antibody blocking type 1 interferon receptor C57BL/6 mice model for drug effect evaluation. Methods: Threeweek-old C57BL/6 mice were injected by 2.5 mg anti-mouse interferon 1 receptor monoclonal antibody before 4×10;PFU dengue 2 virus(DENV-2) challenging. Drugs were given and symptoms were observed each day after infection. Also, virus titer and TNF-α, IL-6 concentration was detected. Histopathological examination was used in the analysis of brain, liver, kidney and spleen. Results: Compared with the model group, lower and more stable viremia was observed in Chinese medicine group.Virus titer remained at 1×10;copies/mL, with no sudden rise. Compared with virus challenge control group and complete control group, increasing restriction of body weight(P<0.05) was observed in Chinese medicine group, but it is still significant higher than positive medicine group(P<0.05). The TNF-α and IL-6 level was lower than model group(P<0.05) at 4 and 6 days post infection respectively. The pathological analysis of brain and kidney showed that the lesions in the positive medicine group was the most serious, followed by the model group, and the least severe in the Chinese medicine group. Conclusion:The virus titer is relatively mild while using dengue optimized prescription. Using this drugs can also prevent high level of inflammatory factor in mouse.