Objective: To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.
Methods: A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.
Results: Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).
Conclusion: Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.
目的：观察麦粒灸对甲状腺功能减退症伴抑郁状态大鼠行为学、血清五羟色胺（5-HT）、皮质醇和海马盐皮质激素受体（MR）、糖皮质激素受体（GR）的影响，探究麦粒灸改善甲状腺功能减退症大鼠抑郁状态的可能机制。方法：将32只SPF级SD大鼠随机分为空白组、模型组、西药组和麦粒灸组，每组8只。除空白组外，其余大鼠用0.1%丙基硫氧嘧啶（PTU）混悬液按1 mL/100 g灌胃，每日1次，共4周，以制备甲状腺功能减退症大鼠模型，并通过行为学判定大鼠是否伴随抑郁状态。西药组采用左旋甲状腺素钠（优甲乐）0.9 mL/100 g灌胃，每日1次，共4周；麦粒灸组于“大椎”“命门”“肾俞”“脾俞”行麦粒灸，每穴灸7壮，每日1次，每周6次，共4周。干预结束后，行为学实验观察各组大鼠抑郁情况；ELISA法检测血清促甲状腺激素（TSH）、总甲状腺素（TT4）、5-HT和皮质醇的含量；Western blot法检测大鼠海马MR、GR蛋白表达；实时荧光定量PCR法检测大鼠海马MR、GR mRNA表达。结果：干预前，与空白组比较，其余3组大鼠旷场实验（OFT）评分下降、悬尾实验（TST）不动时间延长（P<0.05）；血清TSH含量上升、TT4含量下降（P<0.01）。干预后，与模型组比较，西药组大鼠OFT垂直得分升高、强迫游泳实验（FST）不动时间延长（P<0.05），麦粒灸组大鼠OFT 3项得分均升高（P<0.05，P<0.01），TST和FST不动时间缩短（P<0.01，P<0.05）；与西药组比较，麦粒灸组大鼠TST和FST不动时间缩短（P<0.05，P<0.01）。与空白组比较，模型组大鼠血清TSH、皮质醇含量上升（P<0.01，P<0.001），TT4、5-HT含量下降（P<0.01，P<0.001）；与模型组比较，西药组和麦粒灸组大鼠血清TT4和5-HT含量上升、TSH和皮质醇含量下降（P<0.01，P<0.05）。与空白组比较，模型组大鼠海马MR、GR mRNA及蛋白表达均减少（P<0.01，P<0.05，P<0.001）；与模型组比较，西药组大鼠海马MR mRNA和蛋白表达上升（P<0.05），麦粒灸组大鼠海马MR、GR蛋白及MR mRNA表达均升高（P<0.05，P<0.01）；与西药组比较，麦粒灸组大鼠海马MR mRNA表达升高（P<0.05）。结论：麦粒灸可明显改善甲状腺功能减退症模型大鼠的甲状腺功能和抑郁状态，其机制可能与上调海马MR、GR的蛋白和mRNA表达，进而影响血清皮质醇和5-HT表达有关。.
Keywords: depression; glucocorticoid receptor (GR); hippocampus; hypothyroidism; mineralocorticoid receptor (MR); wheat-grain moxibustion.