淫羊藿減輕激素抑制HPAT軸的實驗與臨床

An Approach to Epimedium Antagonized the Glucocorticoid Side-Effect on Hypothalamus- Pituitary-Adrenal-Thymus Axis

神經內分泌免疫網絡的研究是目前國際醫學領域的新興課題，在中國有關這方面的研究不少。為探討補腎藥減輕糖皮質激素（Glucocorticoid）副作用的實驗與臨床效應，本文觀察了補腎要藥-“淫羊藿”對外源性糖皮質激素抑制下丘腦- 垂體- 腎上腺- 免疫軸（HPAT 軸）的影響， _結果如下： _ 1. 大鼠連續14 天皮下注射皮質酮（10 mg/kg 體重）時，HPAT 軸出現明顯抑制，垂體、腎上腺、胸腺重量減輕；下丘腦單胺類遞質活動增強，NE、DA、DOPAC、5-HT、5-HIAA等含量升高；下丘腦室旁核CRF 神經細胞及正中隆起CRF 神經纖維和垂體前葉ACTH 分泌細胞減少，腎上腺皮質及胸腺萎縮；血漿ACTH、皮質酮含量下降；淋巴細胞增殖反應及自然殺傷細胞活性降低，ConA 誘導的 _T 淋巴細胞產生γ-IFN 和IL-2 能力減弱等。 2. 大鼠連續14 天用淫羊藿水提取液灌胃（10g/kg 體重）可以有效改善外源性糖皮激素對下丘腦- 垂體- 腎上腺- 免疫的抑制。與模型組比較，淫羊藿組下丘腦室旁核CRF 神經細胞及正中隆起神經纖維和垂體前葉ACTH 細胞學免疫組化染色加深，數量增多，腎上腺皮質束狀帶及胸腺萎縮現象得到改善；下丘腦單胺類遞質含量下降，垂體、腎上腺、胸腺重量增加；血漿ACTH，皮質酮含量升高；淋巴細胞增殖反應與自然殺傷細胞活性明顯增強，ConA 誘導T 淋巴細胞誘生γ-IFN 和 _IL-2 能力顯著升高（P<0.05）。 3. 為觀察淫羊藿對長期服用強的松（prednison）患者的影響，我們選擇每日服用強的松20mg 以上，服用時間1 個月以上的患者30 例，對照組與治療組各15 例。對照組為服用單純強的松片，每片含強的松5mg，治療組服“仙靈強的松膠囊”，每膠囊含強的松5mg，淫羊藿提取物5g，療程均為1 個月。觀察治療前後兩組患者的血漿ACTH、皮質醇水平與外周血淋巴細胞增殖反應。結果表明：對照組用藥後血漿ACTH、皮質醇及淋巴細胞增殖反應較用藥前呈下降趨勢（P<0.05）。治療組在改善臨床症狀的同時，上述指標的下降趨勢亦得到明顯保護， _治療前後無顯著差異（P<0.05）。作者認為：淫羊藿可能通過補腎而改善外源性糖皮質激素對HPAT 軸的抑制，進一步支持腎虛本質之一為-“HPAT 軸功能低下”的觀點。 Currently the research into the neuroendocrinic immunal network is in full swing elsewhere in the world, while it also be just unfolding in china, in order to observe tonifying kidney medicines clinical and laboratory effectiveness in reducing the side-effects of GC, our study takes a comprehensive and systematic look at the effect of EP on external GC's inhibition of the HPAT immune axis, the results showed: 1. After 14 days of subcutaneous corticosterone (CORT) 10 mg/kg injection, the HPAT axis showed obvious restraint, the weights of thymus and the pituitary and adrenal glands decreased, there is increase in the activity of hypothalamus monoamine transmitters, while the level of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylanine (DOPAC), 5-hydroxyindole acetic acid (5-HIAA), and serotonin (5-HT) showed increase. The CRF neurocytes in paraventricular nucleus (PVN), CRF neurofibril in median eminence (ME) and ATCH secreatocytes in anterior pituitary all showed decrease. Atrophy is found in adrenal gland and in thymus. There is decrease in levels of ACTH and CORT in blood, lymphocytic proliferation reaction and Natural-Killer Cell Cytotoxicity (NKCC) activity decreased, while ConA induced T-lymphocyte's IL-2 and γ-IFN production capabilities showed decrease. 2. Continual oral ingestion of EP for 14 days in rats 10mg/kg can effectively relieve the inhibition of external GC on HPAT axis. Compared with the model group, in EP group the numbers of CRF neurocytes showed icrease, while their immunohistochemistry staining is darker. The atrophied cortex of the adrenal gland showed improvement, the lymphocytic proliferation reaction and NKCC activity showed obvious increase, while ConA induced T-lymphocyte's IL-2 and γ-IFN production capabilities showed dramatic increase (P<0.05). 3. In order to observe the effect of EP on patients who took prednisone for a long time, we chose 30 patients who took prednisone >20mg/d for longer than one month. 15 cases in treatment group and control group respectively. Patients in control group took one 5 mg prednisone tablet; patients in treatment group took “xianling prednisone capsule” (which contains 5 mg each of prednisone and EP). Treatment time was one month. Observing the clinic