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目的:优化芍药甘草汤治疗高泌乳素血症(HPRL)的组方,并对其疗效机制进行初步探讨。方法:60只雌性NIH小鼠,随机分为6组,每组10只。除10只为空白组、仅进行生理盐水灌胃外,其他5组均经甲氧氯普胺连续皮下注射50天获得HPRL小鼠动物模型,随后再随机分配治疗方案:芍药甘草汤-1、2、3组(SG-1、2、3),分别给予1∶3、1∶1及3∶1芍药/甘草配比的芍药甘草汤,阳性对照组给予溴隐亭,模型组给予生理盐水;均连续灌胃30天。以ELISA法比较不同药物对血清泌乳素(PRL)水平的影响;同时观察血清卵泡刺激素(FSH)、促黄体生成素(LH)、睾酮(T)、雌二醇(E2)水平的改变;并以定量PCR法检测垂体表达泌乳素(Prl)m RNA、泌乳素调节元件结合蛋白(Preb)m RNA的改变。结果:造模后50只小鼠的PRL明显升高,FSH、LH、T和E2均明显降低(均P<0.01)。阳性对照组经溴隐亭治疗后,PRL明显降低,FSH、LH和E2均明显提高(均P<0.05)。SG-1、2、3组的PRL均较模型组有明显降低(均P<0.05),但仅SG-3组与阳性对照组的差异无统计学意义(P>0.05)。此外,SG-2、SG-3组治疗后血清FSH升高(P<0.05)、而T、LH、E2的改变不明显。SG-1、2、3组均可使垂体Prl m RNA显著降低(均为P<0.01)。SG-2、3组还可见Preb m RNA显著降低(分别为P<0.05和P<0.01)。结论:芍药甘草汤能有效降低甲氧氯普胺注射小鼠的血清泌乳素的水平,且重用芍药效果最明显;其机制可能与升高FSH、抑制垂体Prl、Preb m RNA的表达有关。
OBJECTIVE: To optimize the prescription of Shaoyao Gancao Decoction in the treatment of hyperprolactinemia (HPRL) and to investigate its therapeutic mechanism. Methods: Sixty female NIH mice were randomly divided into 6 groups with 10 rats in each group. Except 10 rats in the blank group, rats in the other 5 groups were given subcutaneous injection of metoclopramide for 50 days to get the animal model of HPRL mice, then randomly assigned the treatment program: Shaoyao Gancao Decoction-1, Groups 2 and 3 (SG-1, 2 and 3) were given Paeonia and Glycyrrhiza cones with ratio of 1: 3, 1: 1 and 3: 1 respectively. Bromocriptine was given to the positive control group and normal saline ; Were continuous gavage for 30 days. The effects of different drugs on serum prolactin (PRL) levels were compared by ELISA. At the same time, the changes of serum FSH, LH, T and E2 were observed. The changes of pituitary prolactin (Prl) m RNA and prolactin regulatory element binding protein (Preb) m RNA were detected by quantitative PCR. Results: After modeling, the PRL of 50 mice were significantly increased, FSH, LH, T and E2 were significantly decreased (all P <0.01). The positive control group after bromocriptine treatment, PRL decreased significantly, FSH, LH and E2 were significantly increased (all P <0.05). SGL-3 group and PRL group were significantly lower than the model group (all P <0.05), but only the SG-3 group and the positive control group, the difference was not statistically significant (P> 0.05). In addition, serum FSH in SG-2 and SG-3 groups increased (P <0.05), while changes in T, LH and E2 were insignificant. Pituitary Prl m RNA was significantly decreased in SG-1, 2 and 3 groups (both P <0.01). The levels of Preb m RNA in SG-2 and 3 groups were also significantly lower (P <0.05 and P <0.01, respectively). Conclusion: Shaoyao Gancao Decoction can effectively reduce the level of prolactin in mice injected with metoclopramide, and the effect of reusing peony is the most obvious. The mechanism may be related to increasing FSH and inhibiting the expression of Pr1 and Preb m RNA in pituitary.