rhIL-6促进血小板恢复的优化应用条件的研究

Study on optimal admimstration conditions of rhIL 6 for accelerating blood platelet recovery in irradiated mice

目的：研究不同给药条件对ｒｈＩＬ－６药效的影响，优化给药方式。方法：以γ射线照射６．５Ｇｙ的ＬＡＣＡ小鼠为造血系统损伤模型，分别按不同的给药途径（皮下或腹腔注射）、每日次数（每天１次或分２次给药）、每日剂量（５００μｇ·ｋｇ－１·ｄ－１×４，２５０μｇ·ｋｇ－１·ｄ－１×８）和开始治疗时间（照后３０ｍｉｎ、１２ｈ、２４ｈ和７２ｈ）等给ｒｈＩＬ－６，观察照后第１１、１４、１８和２２天外周血细胞数的变化。结果：发现ｒｈＩＬ－６采用每日２次皮下注射给药时血小板数显著高于对照组，亦高于每日１次皮下注射组和每日２次腹腔注射组；在有效剂量范围内和总给药剂量相同时，降低每日给药剂量相应延长给药时间并不降低ｒｈＩＬ－６的药效；ｒｈＩＬ－６不同开始治疗时间各组血小板（ＰＬＴ）升高幅度依次为照后１２ｈ、３０ｍｉｎ、２４ｈ和７２ｈ，其中２４ｈ前３个给药组血小板数比对照组升高有统计学意义。结论：ｒｈＩＬ－６促血小板生成较佳的条件是在照射后２４ｈ内（最好在照后１２ｈ）给药，每日２次皮下注射；当给药剂量较大时，可采用减少每日剂量，延长给药时间方案。

Objective: To study the influence of administration conditions on the efficacy of rhIL 6. Methods: In 6.5 Gy gamma irradiated LACA mice, rhIL 6 500 μg·kg -1 ·d -1 ×4(sc or ip, 2/d or 1/d) was started at 30 min, 12 h, 24 h or 72 h after irradiation, and in one group 8 day treatment was given(250 μg·kg -1 ·d -1 ×8). The peripheral PLT, WBC and RBC counts were determined on days 11, 14, 18 and 22. Results: It was shown that the peripheral PLT counts in sc 2/d, sc 1/d and ip 2/d rhIL 6 treated groups were higher than that of the control, with the sc 2/d group showing the best recovery of platelet. The 8 day treatment group showed a PLT recovery accelerating effect similar to that of the 4 day treatment group. In the study on the effect of starting time of administration, there was no statistically significant difference between the PLT counts of +30 min and +12 h groups although higher in +12 h group. The PLT counts in both of these two groups were significantly higher than that in +72 h group and those in +30 min, +12 h and +24 h groups were significantly higher than that in the control. Conclusion: rhIL 6 should be administrated sc bid from within 24 h postirradiation and is better to start at +12 h. When total dose of rhIL 6 is large, it is better to reduce the daily dose together with prolonging the duration of treatment in order to reduce side effects.