乳癖散结胶囊对丙基硫氧嘧啶致大鼠甲状腺肿大的作用

Effect of Rupi Sanjie Capsules on rat goiter induced by propylthiouracil

目的 探讨乳癖散结胶囊对丙基硫氧嘧啶(propylthiouracil,PTU)致甲状腺肿大模型大鼠的治疗作用。方法 选取60只SD大鼠,随机分为对照组,模型组,优甲乐组(0.02 mg·kg^(-1)),乳癖散结低、中、高剂量组(0.5、1.0、2.0 g·kg^(-1)),每组10只,雌雄各半;除对照组外,其余5组每日灌胃10 mg·kg^(-1) PTU,连续干预2周,构建甲状腺肿大病理模型;2周后,改为隔日灌胃PTU,除对照组及模型组外,各给药组每日给予不同剂量药物,连续给药4周,每周称体质量。第6周时,末次给药后次日股动脉采血,通过酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)测定血清游离三碘甲状腺原氨酸(free triiodothyronine,FT_3)、游离四碘甲状腺原氨酸(free tetraiodothyronine,FT_4)和促甲状腺激素(thyroid stimulating hormone,TSH)含量;剖取甲状腺,计算甲状腺系数;用苏木精-伊红(hematoxylin-eosin,HE)染色法观察各组大鼠甲状腺病理学变化。结果 6周内,对照组大鼠体质量增长明显;与对照组相比,模型组体质量增长显著减缓(P<0.05),与模型组相比,乳癖散结低、中、高剂量组大鼠体质量增长改善,尤其雌鼠体质量恢复至与对照组无显著差异;优甲乐组雄鼠较模型组体质量增长显著改善,与对照组比较差异无统计学意义。对照组大鼠甲状腺系数均处于正常生理范围,而模型组明显升高(P<0.01);与模型组比较,药物改善组甲状腺指数均显著降低(P<0.05)。与对照组比较,模型组FT_3、FT_4水平略有降低,TSH水平略升高,趋于紊乱状态;与模型组相比,乳癖散结低、中、高剂量组治疗4周后FT_3、FT_4和TSH水平均趋于正常生理值。HE染色结果显示,模型组大鼠甲状腺结构明显损伤,上皮细胞显著增生,部分滤泡呈空泡状,乳头状体突入泡腔,泡状大小不均,胶质含量减少。与模型组比较,各受试药物组甲状腺组织滤泡结构明显改善,上皮细胞肿胀和乳突状增生减少,其中乳癖散结高、中剂量组甲状腺滤泡结构萎缩改善明显,滤泡腔增大,上皮细胞增生改善。结论 乳癖散结胶囊1~2 g·kg^(-1)连续灌胃4周对PTU致大鼠甲状腺肿有一定治疗作用。

Objective To observe the effect of Rupi Sanjie Capsules on propylthiouracil(PTU)induced goiter in rats.Methods Sixty SD rats were randomly divided into control group,model group,levothyroxine sodium positive group(0.02 mg·kg^(−1)),Rupi Sanjie Capsules low,medium and high dose groups(0.5,1,2 g·kg^(−1)),with 10 rats in each group,half male and female.All groups,except for the control group,were administered by gavage with 10 mg·kg^(−1) PTU to establish the pathological model of goiter,once a day for 2 weeks.Two weeks later,all rats in each group except for the control group were given PTU once every 2 days to maintain the pathological changes.The positive group and Rupi Sanjie group were given different drugs once a day for 4 weeks.The body weight was observed every week.At week 6,the blood was collected from the femoral artery of the rats following their last administration.Thyroid glands were dissected and weighed,and the thyroid coefficient was calculated.The contents of free triiodothyronine(FT3),free tetraiodothyronine(FT4)and thyroid stimulating hormone(TSH)in serum were determined by enzyme linked immunosorbent assay(ELISA).The histopathological changes were observed by HE staining.Results Within 6 weeks,the body weight of rats in the normal control group increased normally;Compared with the control group,the weight gain of the model group was significantly slowed down(P<0.05),while compared with the model group,the body weight growth of the low,medium and high dose Rupi Sanjie groups was improved,especially the body weight of the female rats recovered to the same level as the control group.The thyroid coefficients of rats in the control group were in the normal physiological range,while those in the model group were significantly increased(P<0.01).Compared with the model group,the thyroid index of the drug improvement group was significantly decreased(P<0.05).Compared with the control group,the levels of FT3 and FT4 in the model group were slightly lower,and the level of TSH was slightly higher,which tended to be disordered.Compared with the model group,the levels of FT3,FT4 and TSH in the Rupi Sanjie low,medium and high dose groups tended to normal physiological values after 4 weeks of treatment.HE staining showed that the thyroid structure of the model group was obviously damaged,the epithelial cells were significantly proliferated,some follicles were vacuolated,the papillary body protrude into the bubble cavity,the size of the bubble was uneven,and the colloid content was reduced.Compared with the model group,the thyroid follicular structure was significantly improved,epithelial cell swelling and mastoid hyperplasia were reduced in the test drug groups,and the atrophy of thyroid follicular structure was significantly improved,the follicular cavity was enlarged,and epithelial cell proliferation was improved in the high and medium dose Rupi Sanjie Capsules groups.Conclusion Rupi Sanjie Capsules,administered by gavage at a dosage of 1-2 g·kg^(−1) for a continuous period of 4 weeks,exerts a therapeutic efficacy against PTU-induced goiter in rats.