缓释醋酸亮丙瑞林微球对大鼠子宫异位内膜的抑制作用

目的: 观察国内研制的醋酸亮丙瑞林微球(LE-ms)对异位子宫内膜的抑制作用,并初步探讨原料药的作用机制。方法: 以手术方法制备子宫内膜异位症(endometriosis,EMT)模型SD 大鼠60只,随机分组给药,并计算各用药组对异位内膜的抑制率。另取SD 大鼠30 只,随机分为假手术组、EMT 模型组、用药组。3 周后,测血清E2 水平;异位内膜体积;子宫、卵巢、胸腺和脾脏重量;NK 细胞活性。结果: 醋酸亮丙瑞林(LE)20 μg·kg^-1、进口LE-ms 20 μg·kg^-1·d^-1,抑制率依次为87.2 %和78.3 %。国产LE-ms 2、20、200 μg·kg^-1·d^-1对大鼠异位内膜抑制率依次为57.3 %、89.0 %和94.7 %。LE 可使EMT 大鼠动情周期消失;血清E₂ 水平降低;子宫重量明显减轻;胸腺重量明显增加和NK 细胞活性明显提高。结论: 国内研制的醋酸亮丙瑞林微球疗效与相同剂量的进口同类产品及原料药的作用相当,其作用机制可能是抑制大鼠性腺轴系并通过拮抗雌激素作用来提高EMT 大鼠的免疫功能。

Inhibitory effects of leuprolide acetate microsphere on experimentally induced endometriosis in rats

AIM: To study the inhibitory effects of domestic leuprolide acetate microsphere (LE-ms)on the growth of explanted endometrium in the rat models of EMT and its possible mechanisms.METHODS: The 60 rats models of EMT were induced surgically by the Jones method.Then the animals were treated with LE (20μg·^-1 ·d^-1, 28 d, sc), enanton(20 μg·^-1·d^-1, sc)and domestic LE-ms (2, 20, and 200 μg㎏^-1 ·d^-1, sc), respectively;another 30 rats were divided into sham group(N.S, 1 ml·kg^-1·d^-1, 21 d, sc), EMT + LE group(100 μg·kg^-1·d^-1, 21 d, sc)and EMT group(N.S, 1ml·kg^-1·d^-1, 21 d, sc).At the same time, estrous cycle was monitored daily by examination of vaginal cytologic smears.After 3 weeks, blood was drawn and the serum estradiol concentration was assayed.The volume of endometrial implant was assessed.Lateral uterus, bilateral ovary, thymus and spleen were weighed.The NK cell cytotoxicity in the spleen was evaluated with lactate dehydrogenase (LDH)release assay.RESULTS: Implants in control group continued to grow, while those in groups treated with the drugs showed remarkable atrophy.The inhibitory rates were 87.2 %, 78.3 %, 57.3 %, 89.0 % and 94.7 %, respectively.The regular estrous cycle of the model rats was abolished and serum estradiol reduced(P<0.05);the lateral uterine weight was reduced significantly(P<0.001);the thymus weight was increased(P<0.05);the spleen weight did not change significantly(P>0.05);and the NK cells activity was enhanced(P<0.05).CONCLUSION: Ectopic endometrium can be inhibited significantly with the treatment of domestic leuprolide microsphere, and its mechanism may be related to reduce estrogen level, which is important for both the growth of the ectopic endometrium and the enhancement of immune function.