荔枝核黄酮类化合物对小鼠Ⅰ型单纯疱疹病毒性脑炎的作用及机制

发布时间：2018-10-15 20:39

【摘要】：目的探讨荔枝核黄酮类化合物(FLCS)对体外抗Ⅰ型单纯疱疹病毒(HSV-1)的作用及其可能机制,进一步验证该药对小鼠病毒性脑炎的治疗效果,从而为HSV-1感染的治疗提供新的手段。方法采用微量细胞培养法和MTT比色法观察FLCS对HSV-1感染细胞的保护作用,通过检测细胞病变效应(CPE)以及病毒抑制率确定该药体外抗病毒活性。进一步利用小鼠病毒性脑炎模型,设计治疗方案(FLCS 3个剂量组,疗程5 d),观察小鼠生存率、平均存活时间、组织中病毒滴度,评价FLCS对小鼠病毒性脑炎的治疗作用。结果 FLCS不仅对HSV-1有直接灭活作用,而且还可阻止HSV-1的生物合成,表现为各剂量组FLCS通过不同方式和病毒作用后,HSV-1感染细胞的PE则随药物浓度的增加而减少,病毒抑制率明显升高。FLCS对HSV-1直接灭活作用和抑制生物合成作用的细胞半数抑制有效浓度(IC50)分别为32.76μg/mL和12.72μg/mL,相应作用方式的治疗指数(TI)分别为7.3和18.8。但是FLCS不能阻止HSV-1吸附细胞,表现为各剂量组FLCS作用细胞后,HSV-1再感染细胞,均出现典型CPE。对于小鼠来说,其体征大多数都会从厌食、呆滞以及嗜睡等症状,逐渐转变为颤抖、抖毛、背弓、抽搐、打转、体重下降等神经系统感染症状,直至死亡,FLCS治疗组小鼠组织病变程度减轻。结论FLCS虽不能阻止病毒吸附与穿入易感细胞,但能直接杀灭病毒以及抑制HSV-1的生物合成或(和)以后环节发挥其抗病毒作用。FLCS能降低HSV-1感染小鼠死亡率,延长平均生存期,加快组织中病毒的清除,缓解小鼠脑炎症状。
[Abstract]:Objective to investigate the anti-herpes simplex virus type I (HSV-1) effect and its possible mechanism of lichee seed flavonoid compound (FLCS) in vitro, to further verify the therapeutic effect of this drug on viral encephalitis in mice, and to provide a new method for the treatment of HSV-1 infection. Methods Microcell culture and MTT colorimetry were used to observe the protective effect of FLCS on HSV-1 infected cells. The antiviral activity of FLCS was determined by detecting the cytopathic effect (CPE) and virus inhibition rate in vitro. In order to evaluate the therapeutic effect of FLCS on viral encephalitis in mice, the survival rate, mean survival time and virus titer in tissues were observed for 5 d), by using the model of mouse viral encephalitis (FLCS). Results FLCS could not only inactivate HSV-1 directly, but also prevent the biosynthesis of HSV-1. The results showed that the PE of HSV-1 infected cells decreased with the increase of drug concentration after the treatment of FLCS in different ways and virus. The inhibition rate of virus was significantly increased. The IC50 of the cells with direct inactivation of HSV-1 and inhibition of biosynthesis with FLCS were 32.76 渭 g/mL and 12.72 渭 g / mL, respectively. The treatment index (TI) of the corresponding mode of action was 7.3 and 18.8 respectively. However, FLCS could not prevent HSV-1 cells from being adsorbed. It was shown that after the cells were treated with FLCS in different dosage groups, HSV-1 reinfected the cells, and all of them appeared typical CPE.. For mice, most of their signs change from anorexia, stagnation and lethargy to symptoms of nervous system infections such as tremors, shakes, back bows, convulsions, twists, weight loss, etc. Until death, the degree of pathological changes in FLCS treated mice was alleviated. Conclusion although FLCS can not prevent the virus from adsorbing and penetrating into susceptible cells, it can kill the virus directly and inhibit the biosynthesis of HSV-1 or / or exert its antiviral effect in later stages. FLCS can reduce the death rate and prolong the average survival time of mice infected with HSV-1. Speed up the clearance of the virus in the tissue, relieve the symptoms of encephalitis in mice.
【作者单位】：河南中医药大学第二临床医学院急诊科;郑荣医院普内科;
【分类号】：R512.3

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