肝郁、脾虚和肝郁脾虚证模型大鼠下丘脑-垂体-甲状腺轴功能的变化及柴疏四君子汤的作用

Changes of Thyroid Function in Different Rat Models of Liver-stagnation Syndrome,Spleen-deficiency Syndrome and Combining Liver-stagnation and Spleen-deficiency Syndrome and the Effect of Applying the Chaishu Sijunzi Decoction

目的:比较肝郁、脾虚和肝郁脾虚模型大鼠甲状腺功能的变化及应用疏肝健脾方后的效用。方法:大鼠随机分为正常对照组、肝郁组、脾虚组、肝郁脾虚组、肝郁柴疏四君子汤组(肝郁治疗组)、脾虚柴疏四君子汤组(脾虚治疗组)、肝郁脾虚柴疏四君子汤组(肝郁脾虚治疗组)7组,每组10只。肝郁组、脾虚组、肝郁脾虚组及其各治疗组大鼠分别采用慢性束缚、过度疲劳+饮食失节、慢性束缚+过度疲劳+饮食失节法造模,正常对照组不予处理;3个模型治疗组分别于造模第2周末(即造模第15天起),按3.57 g·kg-1给予大鼠柴疏四君子汤颗粒灌胃,连续2周;各模型组和正常对照组给予等量蒸馏水。实验第29天,测定各组大鼠血清三碘甲腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、血清和下丘脑促甲状腺激素释放激素(TRH)。结果:与正常组相比,肝郁组、脾虚组和肝郁脾虚组大鼠血清T3,T4,TRH均显著降低(P<0.05),TSH均显著升高(P<0.05);脾虚组和肝郁脾虚组大鼠下丘脑TRH均显著降低(P<0.05);肝郁组大鼠下丘脑TRH无明显变化。与肝郁组相比,肝郁柴疏四君子汤治疗组大鼠血清T4显著升高(P<0.05),TSH显著降低(P<0.05),血清T3TRH和下丘脑TRH无明显变化;与脾虚组相比,脾虚柴疏四君子汤治疗组大鼠血清T3显著升高(P<0.05),TSH显著降低(P<0.05),下丘脑TRH有升高趋势,血清T4,TRH无明显变化;与肝郁脾虚组相比,肝郁脾虚柴疏四君子汤治疗组大鼠血清T3,下丘脑TRH均显著升高(P<0.05),血清TSH显著降低(P<0.05),血清T4,TRH无明显变化。结论:肝郁、脾虚、肝郁脾虚三证模型大鼠存在甲状腺功能减低并伴有下丘脑-垂体-甲状腺轴调节异常,其中肝郁证存在下丘脑TRH的释放障碍,脾虚和肝郁脾虚则同时还存在TRH合成的抑制。柴疏四君子汤对3个证候模型的甲状腺功能及其轴调节具有一定的改善作用,但以对肝郁脾虚证的作用最优。

Objective： To Compare the changes of different rat models of liver-stagnation syndrome, spleen-deficiency syndrome and both liver-stagnation and spleen-deficiency syndrome with thyroid function and study on the effective of application soothing liver Qi and tonifying spleen Qi formula to those rat models. Method ： The male wistar rats were randomly assigned into the normal group （group 1 ） , the liver-stagnation group （group 2） , the spleen-deficiency group （group 3 ） , the liver-stagnation and spleen-deficiency group （group 4） , the drug treatment to liver-stagnation group （ group 5 ）, the drug treatment to spleen-deficiency group （ group 6） and the drug treatment to liver-stagnation and spleen-deficiency group （group 7） with ten rats for each group. The models were established by chronic restraint method in group 2 and 5, by excess fatigue plus out of constant diet method in group 3 and 6, by chronic restraint-fatigue-diet disorder method in group 4 and 7 for 4 weeks. On the 15th day, rats of group 5, 6 and 7 had been fed with medicine of Chaishu Sijunzi decoction 3.57 g.kg-1 for two weeks. The ones of the normal group and model group 2, 3 and 4 were fed with equivalent physiological saline for two weeks. On the 29Lh day, all rats of serum levels of 3, 5, 3＇-triiodothyronine （T3） , thyroxin, 3, 5, 3, 5＇-tetraiodothyronine （T4）, thyroid stimulating hormone （TSH） and both of serum and hypothalamus tyrotropin releasing hormone （TRH） were detected. Result： Compared with group 1, serum T3, T4 and TRH decreased significantly and serum TSH increased significantly in group 2, 3 and 4 （P 〈 0.05） , hypothalamus TRH decreased significantly in group 3 and 4 （P 〈 0. 05） , hypothalamus TRH had no significantly changing in group 2. Compared with group 2, serum T4 increased significantly and serum TSH decreased significantly in group 5 （P 〈 0.05）. Compared with group 3, serum T3 increased significantly and serum TSH decreased significantly in group 6 （P 〈 0.05 ） and hypothalamus TRH had increasing tendency in group 6. Compared with group 4, serum T3 and hypothalamus TRH increased significantly and serum TSH decreased significantly in group 7 （P 〈 0.05） and serumT4 had increasing tendency in group 6. Conclusion： The function of hypothalamus-ptuitary-thyroidal axis was abnormal at different degrees in rat models of liver-stagnation syndrome, spleen-deficiency syndrome and both liver-stagnation and spleen-deficiency syndrome with hypothyroidism. Liver-stagnation syndrome was mainly involved the function of releasing impairment with hypothalamus TRH. Both of spleen-deficiency and liver-stagnation and spleen-deficiency syndromes were not only involved in releasing impairment, but also involved in synthesis restraining with hypothalamus TRH. The formula of soothing liver Qi and tonifying spleen Qi can improved the function of thyroid gland and thyroidal axis to those rat models; however the best improvement of comprehensive regulating function was to liver-stagnation and spleen-deficiency syndrome model.