雷公藤多苷不同给药方式对雌性大鼠肝功能及生殖功能影响的比较研究

Comparison of Influence on Liver Function and Reproductive Function of Different Administration of Tripterygium Glycosides

[目的]观察雷公藤多苷(Tripterygium glycosides,TG)连续和间歇给药对大鼠肝功能和生殖功能的不同影响。[方法]将60只成年SD大鼠随机分成3组,每组20只,间歇给药组大鼠间歇以临床等效剂量20mg/kg·d的TG混悬液灌胃,每周连续给药4d,其后3d以等容量0.9%氯化钠溶液灌胃;连续给药组大鼠连续以临床等效剂量20mg/kg·d的TG混悬液灌胃,每日给药;空白对照组大鼠每天以等容量0.9%氯化钠溶液灌胃,当两给药组大鼠给药累积量达到800mg·kg^(-1)和1 400mg·kg^(-1)两个阶段,分别检测谷丙转氨酶(alanine transaminase,ALT)、天冬氨酸氨基转移酶(aspartate transaminase,AST)水平,并行阴道涂片观察动情周期,同时以ELISA法测定血清卵泡刺激素(follicle-stimulating hormone,FSH)与黄体生成素(luteinizing hormone,LH)水平。[结果]雷公藤多苷累积剂量达到800mg·kg^(-1)时,两给药组ALT、AST水平均较同时期空白对照组明显升高,差异有统计学意义(P<0.05),但两给药组之间差异无统计学意义(P>0.05);两给药组均有部分大鼠动情周期延长,而连续给药组出现动情周期延长的比例较高于间歇给药组,延长时间也长于间歇给药组,差异均有统计学意义(P<0.05);两给药组大鼠卵巢、子宫指数均较空白对照组明显下降,差异有统计学意义(P<0.05),但两给药组之间差异无统计学意义(P>0.05);两给药组FSH/LH值均高于空白对照组,差异有统计学意义(P<0.05),其中间歇给药组增高幅度低于连续给药组(P<0.05)。当累积剂量达1 400mg·kg^(-1)时,两给药组大鼠的ALT、AST水平均较同时期空白对照组显著升高(P<0.01),而且连续给药组ALT、AST水平较间歇给药组升高更为显著(P<0.05);两给药组大鼠动情周期均有延长且不规则,间歇给药组动情周期消失大鼠比例显著少于连续给药组(P<0.05);两给药组大鼠卵巢、子宫指数均明显低于空白对照组(P<0.01),其中连续给药组较间歇给药组下降更为显著(P<0.01);两给药组大鼠FSH/LH值均较前进一步升高,而间歇给药组FSH/LHS值低于连续给药组(P<0.01)。[结论]同等剂量下,TG间歇给药方案对肝功能、生殖功能的损害比传统连续给药方案轻微。

[Objective] To observe the intermittent therapy of Tripterygium glycosides(TG) influence to the liver and reproductive function of the female SD rats. [Methods] Sixty estrus SD rats were divided into three groups randomly, the rats in intermittent therapy group were gave equivalent dose of TG suspension intermittently, the rats in continuous therapy group were gave equivalent dose of TG suspension continuously, and the rats in the blank control group were gave the same volume saline solution everyday. When the cumulative dose of TG reached 800 mg ·kg-1 and 1 400 mg·kg-1, alanine transaminase(ALT) and aspartate transaminase(AST) were detected by biochemistry analyzer;estrous cycle was observed by vaginal smear, and serum follicle-stimulating hormone(FSH) and luteinizing hormone(LH) levels were detected by ELISA method. [Results] When the cumulative dose of TG reached 800 mg·kg-1, the levels of ALT and AST in the intermittent administration group and continuous administration group were similarly( P>0.05), but were significantly higher than blank control group(P <0.05).Meanwhile, the estrous cycle of some rats in two drug-administered groups was prolonged,while continuous administration group had a higher proportion of estrous cycle prolongation, and the prolongation time was also longer( P<0.05). There was no significant difference between the two drug-administered groups upon the ovary and uterus index( P >0.05), but was significantly lower than blank control group(P <0.05). The FSH/LH values of two administration groups were higher than blank control group( P <0.05), and the increase index of intermittent administration group was lower than continuous administration group( P<0.05). When the cumulative dose reached 1 400 mg·kg-1, the ALT and AST levels of the two administration groups were significantly higher than blank control group( P<0.01), and the levels of ALT and AST of continuous administration group were significantly higher than intermittent administration group( P <0.05);the estrous cycle of the two administration groups was prolonged and irregular, and the rats with estrous cycle disappear in intermittent administration group were significantly less than continuous administration group(P<0.05). The ovarian and uterus indexes of the two administration groups were significantly lower than blank control group( P<0.01),but the decrease index of intermittent administration group was more significant( P<0.01);the FSH/LH values of the two administration groups were higher than before, while FSH/LH value of intermittent administration group was lower than continuous administration group( P<0.01). [Conclusion] Intermittent treatment is lower damage on the liver function and reproductive function than the traditional continuous treatment.