CAJ | 학술논문

目的：研究酰米菲肽（ XMT）对慢性不可预见性轻度应激（ CUMS）抑郁模型大鼠行为的影响，并探讨其可能的作用机制。方法60只SD大鼠随机分为6组，分别为正常对照组、模型组、Flu阳性对照组（10 mg/kg ）和XMT高、中、低剂量组（3．0、1．0、0．2 mg/kg）。除正常对照组外，其余采用CUMS＋孤养的方法对大鼠持续应激刺激4周建立抑郁模型，造模成功后给予4周药物治疗。通过糖水偏好实验、旷场实验和体质量称量，观察动物的行为改变，采用酶联免疫法（ELISA）测定大鼠血清中促肾上腺皮质激素（ACTH）及皮质酮（CORT）含量。结果与正常对照组比较，各造模组大鼠经过应激刺激后糖水偏嗜度、自发活动和体质量增长均显著降低（P＜0．05，P＜0．01），血清ACTH和CORT水平显著升高（P＜0．01），呈抑郁样表现。连续给予4周不同剂量的XMT能显著改善由慢性应激所致的大鼠抑郁样行为。与模型组比较，XMT治疗组大鼠的糖水偏嗜度、旷场水平得分及垂直得分、体质量增长显著升高（P＜0．05，P＜0．01），血清ACTH与CORT含量显著降低（P＜0．05，P＜0．01）；与自身给药前数据比较，XMT（3．0、1．0、0．2 mg/kg）组大鼠给药治疗4周后的糖水偏嗜度显著增加（P＜0．05），XMT（3．0、1．0 mg/kg）组大鼠旷场水平得分及垂直得分均显著增加（P＜0．05）。结论 XMT对CUMS抑郁模型大鼠具有抗抑郁样作用，并可抑制慢性应激引起的下丘脑-垂体-肾上腺皮质轴（ HPA）功能亢进。
목적：연구선미비태（ XMT）대만성불가예견성경도응격（ CUMS）억욱모형대서행위적영향，병탐토기가능적작용궤제。방법60지SD대서수궤분위6조，분별위정상대조조、모형조、Flu양성대조조（10 mg/kg ）화XMT고、중、저제량조（3．0、1．0、0．2 mg/kg）。제정상대조조외，기여채용CUMS＋고양적방법대대서지속응격자격4주건립억욱모형，조모성공후급여4주약물치료。통과당수편호실험、광장실험화체질량칭량，관찰동물적행위개변，채용매련면역법（ELISA）측정대서혈청중촉신상선피질격소（ACTH）급피질동（CORT）함량。결과여정상대조조비교，각조모조대서경과응격자격후당수편기도、자발활동화체질량증장균현저강저（P＜0．05，P＜0．01），혈청ACTH화CORT수평현저승고（P＜0．01），정억욱양표현。련속급여4주불동제량적XMT능현저개선유만성응격소치적대서억욱양행위。여모형조비교，XMT치료조대서적당수편기도、광장수평득분급수직득분、체질량증장현저승고（P＜0．05，P＜0．01），혈청ACTH여CORT함량현저강저（P＜0．05，P＜0．01）；여자신급약전수거비교，XMT（3．0、1．0、0．2 mg/kg）조대서급약치료4주후적당수편기도현저증가（P＜0．05），XMT（3．0、1．0 mg/kg）조대서광장수평득분급수직득분균현저증가（P＜0．05）。결론 XMT대CUMS억욱모형대서구유항억욱양작용，병가억제만성응격인기적하구뇌-수체-신상선피질축（ HPA）공능항진。
Objective To study the antidepressant effect of XMT on a chronically unpredictably mildly stressed ( CUMS) depression model in rats and explore its possible mechanism .Methods Sixty male SD rats were randomly divided into six groups as follows:normal control, model, fluoxetine(Flu) positive control (10 mg/kg), XMT of high, middle and low dosages (3.0, 1.0 and 0.2 mg/kg).CUMS and solitary feeding condition were used to establish the rat depression model for 4 weeks, except in normal control group .Then all the rats were administered different drugs for 4 weeks.Sucrose preference test , open-field test and body mass change were measured to assess the behavioral efficacy .The levels of serum ACTH and CORT were determined by ELISA .Results After four weeks of stimulation , compared with normal control group, CUMS depression rats showed depression-like behavior , such as significantly lower sucrose preference , decreased crossing and rearing scores of open-field test, and reduced body mass (P<0.05, P<0.01).The concentration of blood serum ACTH and CORT increased obviously (P<0.01).The treatment with XMT of high, middle and low dosages for 4 weeks could significantly reverse depression-like behaviors induced by CUMS .Compared with model group , the sucrose preference, crossing and rearing scores of open-field test, and body mass were increased obviously in XMT groups ( P<0.05, P<0.01) and the levels of serum ACTH and CORT were significantly improved (P<0.05, P<0.01).Compared with 4 weeks before, the sucrose preference of XMT (3.0, 1.0, 0.2 mg/kg) groups increased obviously (P<0.05), so did the crossing and rearing scores of open-field test of XMT (3.0, 1.0 mg/kg) groups (P<0.05).Conclusion XMT has antidepressant effect on the CUMS depression model in rats , which may be related to suppresing the hypothalamic-pitui-tary-adrenal axis .