HPA轴和RAS系统参与大鼠功能性慢性内脏痛的机制研究

HPA AXIS AND RAS SYSTEM ARE INVOLVED IN THE MECHANISM OF CHRONIC FUNCTIONAL VISCERAL PAIN IN ADULT RATS

目的:观察大鼠功能性慢性内脏痛时下丘脑-垂体-肾上腺(hypothalamic-pituitaryadrenocortical,HPA)轴及肾素-血管紧张素-醛固酮(RAS)系统功能改变。方法:新生期SpragueDawley(SD)大鼠,出生一天随机分成四组,正常组雌雄各一组、肠易激综合症(IBS)模型组雌雄各一组,常规饲养至八周成年采用腹壁撤离反射(AWR)评分、痛阈及腹外斜肌放电(EMG)测定评价内脏痛觉敏感性;采用放射性免疫法检测大鼠血中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)以及血管紧张素I(Ang I)、血管紧张素II(Ang II)和醛固酮含量。结果:(1)与对照组相比,模型组雄、雌大鼠在20、40、60 mm Hg压力下AWR评分和EMG均明显增加(P<0.05);在80 mm Hg压力下,雄性大鼠AWR评分增加,模型组雄、雌大鼠在20、40、60、80 mm Hg压力下痛阈均明显下降(P<0.05);(2)模型组雄性大鼠成年后血中CRH、ACTH、CORT、Ang I、Ang II均明显增加(P<0.05),醛固酮的含量明显减少(P<0.05);雌性中CRH、CORT、Ang II、醛固酮均明显增加(P<0.05)。结论:新生期经历IBS样模型处理后,雄性及雌性大鼠均会导致成年后内脏痛敏的发生,并与HPA轴及RAS系统功能亢进有关。HPA轴及RAS系统的亢进存在一定的性别差异,这种差异可能与自身分泌的雌激素有关。

Objective：To observe the functions of HPA axis and RAS system in chronic functional visceral pain rats.Methods：The neonatal rats were randomly divided into four groups,including male control,female control,male colorectal distension and female colorectal distension.All rats were fed for 8 weeks.Then we used behavioral and electrophysiological methods to evaluate the chronic functional visceral pain of the adult rats after colorectal distension and used radioimmunoassay to evaluate the CRH,ACTH,COTR and Ang Ⅰ,Ang Ⅱ,aldosterone in plasma.Results：（1） In the pressure of 20,40 and 60 mmHg （1 mmHg =0.133 kPa）,irritable bowel syndrome groups presented increased AWR and electromyograph （EMG） of external oblique in both male and female models （P ＜ 0.05） compared with control group.In the pressure of 80 mmHg male irritable bowel syndrome group presented increased AWR,and in the pressure of 20,40,60,80 mmHg decreased pain threshold in both male and female models （P ＜ 0.05,models vs.controls）.（2） The levels of CRH,ACTH,CORT and Ang Ⅰ,Ang Ⅱ increased and aldosterone decreased in male model rats （P ＜ 0.05）,the levels of CRH,CORT,Ang Ⅱ and aldosterone increased in female model rats （P ＜ 0.05）.Conclusion：The male and female rats experiencing colorectal distension in neonatal period can lead to chronic functional visceral pain,HPA axis and RAS system are involved in pathogenesis of chronic functional visceral pain.There are some gender differences between HPA axis and RAS system,and these differences may be related to their secretion of estrogen.