单纯疱疹病毒性角膜炎土贝母皂甙点眼的浓度筛选与刺激性评价

Concentration sift and irritational evaluation of tubeimoside topically given in herpes simplex keratitis

目的 通过动物试验评价土贝母皂甙 (tubeimoside ,Tu)治疗单纯疱疹病毒性角膜炎 (herpessimplexkeratitis ,HSK)的效果及点眼刺激性 ,并确定其点眼浓度值。方法 根据药物的眼刺激性选用 5、2、0 .8、8× 10 -2 、8× 10 -3、8× 10 -4 g·L-1Tu点眼 ,确定 0 .4、0 .2、0 .1g·L-1评价药物疗效。在地鼠肾细胞BHK 2 1上进行单纯疱疹病毒Ⅰ型(HSV 1型 )SM4 4毒株复苏 ,制作兔HSK模型。采用裂隙灯显微镜、扫描电镜和透射电镜观察眼部病变的动态变化评价Tu疗效。结果 5、2 g·L-1Tu有中度刺激性 ,0 .8g·L-1Tu有轻度刺激性。 8× 10 -2 、8× 10 -3、8× 10 -4 g·L-13组Tu无任何眼刺激性。 0 .4g·L-1Tu有轻度刺激性 ,0 .1、0 .2 g·L-1Tu无刺激性。 0 .4、0 .2、0 .1g·L-13组Tu均具有一定疗效。结论 Tu点眼剂的浓度与刺激性呈正相关 ,点眼刺激性从轻度到无的界值浓度为 0 .4、0 .2、0 .1g·L-1。治疗实验性HSK有一定的疗效 。

Objective To appraise the therapeutic and irritational effects of tubeimoside (Tu) on herpes simplex keratitis (HSK) and establish the definite topic value range of concentration by means of animal experiment. Methods According to the ocular irritational effect of tubeimoside on rabbit eyes, 5, 2, 0.8, 8×10 -2, 8×10 -3 and 8×10 -4?g·L -1 were topically given, respectively. Then 0.4, 0.2 and 0.1?g·L -1 Tu were determined to use in the next trial which focused on the tentative evaluation on the therapeutic effect of Tu. HSV-1 (SM 44 strain) was propagated and quantitated on monolayers of BHK-21 cell cultures, then rabbit model of HSK was made after inoculation with scarification. All eyes were examined by slit-lamp-microscopy and corneal samples were observed under transmission and scanning electromicroscope. Results 5, 2?g·L -1 Tu brought about moderate irritation, while 0.8?g·L -1 Tu had a mild irritational effect. No irritating response of any kind could be observed on eyes administered by 8×10 -2, 8×10 -3, 8×10 -4?g·L -1 of Tu. Mild irritation occurred in 0.4?g·L -1 Tu, while no irritational effects appeared in 0.1 and 0.2?g·L -1 Tu. Eyes infected by HSV-1, which were treated by 0.4, 0.2, 0.1?g·L -1 of Tu, responded favorably and similarly. Conclusion Tu concentration had positive correlation with its ocular irritational effect. 0.4, 0.2 and 0.1?g·L -1Tu given topically produced an irritational effect with none to mild degree. Tu, though able to cure experimental HSK to a certain degree, however, has a smaller dramatic effect than acyclovir on HSK.