先天抑郁大鼠内脏敏感性研究

目的 比较先天抑郁Fawn-Hooded(FH/Wjd)大鼠与Sprague-Dawley(SD)大鼠的内脏敏感性,探讨FH/Wjd大鼠作为精神障碍与肠易激综合征共病模型的可行性.方法 采用强迫游泳实验(FST)和糖水实验(SPT)验证FH/Wjd大鼠的抑郁特性.通过腹壁回撤反射(AWR)评估大鼠对不同压力结直肠扩张(CRD)的敏感性.免疫组织化学法检测大鼠结肠5-HT表达水平及结肠、大脑前额叶下边缘皮质(IL)、前边缘皮质(PrL)、前喙扣带回皮质(rACC)区域的c-fos表达水平.结果 FST中FH/Wjd大鼠水中静止时间显著长于SD大鼠(t＝8.931,P＝0.000).SPT中FH/Wjd大鼠糖水饮用量占总饮水量的比例显著低于SD大鼠(t＝4.155,P＝0.001).FH/Wjd大鼠在各CRD压力梯度(20、40、60、80 mm Hg,1 mm Hg=0.133 kPa)下的AWR评分均显著高于SD大鼠(t值分别＝-2.697、-3.464、-6.822、-3.976,P值分别＝0.022、0.006、0.000、0.003).FH/Wjd大鼠对照组结肠5-HT表达水平高于SD大鼠对照组(t=-11.371,P=0.000).FH/Wjd大鼠扩张组和SD大鼠扩张组结肠5-HT表达水平均较各自的对照组上升,且FH/Wjd大鼠表达水平高于SD大鼠(t＝-3.364,P＝0.007).FH/Wjd大鼠对照组和SD大鼠对照组结肠、前额叶各脑区c-fos表达水平差异无统计学意义(结肠:t＝-0.129、P＝0.900;IL:t＝-1.316、P＝0.218;PrL:t＝1.241、P＝0.243;rACC:t＝2.151、P＝0.057).FH/Wjd大鼠扩张组和SD大鼠扩张组结肠与前额叶脑区c-fos 表达水平均较各自的对照组显著上升,且FH/Wjd大鼠表达水平高于SD大鼠(结肠:t＝-5.864、P＝0.000;IL:t＝-2.530、P＝0.030;PrL:t＝-7.039,P＝0.000;rACC:t＝-6.489、P＝0.000).结论 先天抑郁FH/Wjd大鼠存在内脏高敏感性,其肠道高表达5-HT及结肠和大脑IL、PrL、rACC 区域对内脏伤害性刺激的高反应性.有可能作为精神障碍和肠易激综合征共病的动物模型.

Abstract：

Objective To explore the feasibility of inherent depressive Fawn-Hooded (FH/Wjd)rats as a comorbidity model of mental disorder and irritable bowel syndrome (IBS) by comparing visceral sensitivity of FH/Wjd rats and Sprague-Dawley (SD) rats. Methods Depression trait of FH/Wjd rats was validated through forced swimming test (FST) and sucrose preference test (SPT).Visceral sensitivity to colorectal distention (CRD) under various pressures was assessed by abdominal withdrawal reflex (AWR). The expression of 5-HT in rats' colon,c-fos expression in colon and brain areas of infralimbic cortex (IL),prelimbic cortex (PrL) and rostral anterior cingulated cortex (rACC)was tested with immunohistochemistry. Results FST indicated that the immobility time of FH/Wjd rats was significantly longer than that in SD rats (t=-8. 931,P＜0. 01). SPT showed that the ratio of sucrose water in total liquid consumed was significantly lower in FH/Wjd rats than that of SD rats(t=4. 155,P=0. 01). At each CRD pressure gradient (20,40,60 and 80 mm Hg,1 mm Hg=0. 133kPa),AWR score was all significantly higher in FH/Wjd rats than that of SD rats (t=-2. 697,-3.464,-6.822 and -3. 976,P=0. 022,0.006,0.000 and 0.003). The expression level of 5-HT in FH/Wjd rats' control group was significantly higher than that of SD rats' control group (t=-11.371,P=0. 000). Compared with their own control group,5-HT expression increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (t= -3. 364,P= 0. 007). There was no significant difference of c-fos expression in colon and prefrontal brain areas between FH/Wjd rats' control group and SD rats'control group (colon:t=-0. 129,P= 0. 900;IL:t=-1. 316,P= 0. 218;PrL:t=1. 241,P = 0. 243;rACC:t=2. 151,P = 0. 057). Compared with their own control group,the expression of c-fos in colon and prefrontal brain areas significantly increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (colon: t=- 5.864,P= 0.000;IL:t=-2. 530,P = 0. 030;PrL:t=-7. 039,P= 0. 000;rACC:t=-6. 489,P=0. 000). Conclusions Inherent depressive FH/Wjd rats present visceral hypersensitivity. Meanwhile,the expression of 5-HT in colon is high,and with hyperreactivity to visceral noxious stimuli in colon and brain IL,PrL,and rACC areas. FH/Wjd rats might be a comorbidity animal model of mental disorder and IBS.

Study on the visceral sensitivity of inherent depressive rats

Objective To explore the feasibility of inherent depressive Fawn-Hooded (FH/Wjd)rats as a comorbidity model of mental disorder and irritable bowel syndrome (IBS) by comparing visceral sensitivity of FH/Wjd rats and Sprague-Dawley (SD) rats. Methods Depression trait of FH/Wjd rats was validated through forced swimming test (FST) and sucrose preference test (SPT).Visceral sensitivity to colorectal distention (CRD) under various pressures was assessed by abdominal withdrawal reflex (AWR). The expression of 5-HT in rats' colon,c-fos expression in colon and brain areas of infralimbic cortex (IL),prelimbic cortex (PrL) and rostral anterior cingulated cortex (rACC)was tested with immunohistochemistry. Results FST indicated that the immobility time of FH/Wjd rats was significantly longer than that in SD rats (t=-8. 931,P＜0. 01). SPT showed that the ratio of sucrose water in total liquid consumed was significantly lower in FH/Wjd rats than that of SD rats(t=4. 155,P=0. 01). At each CRD pressure gradient (20,40,60 and 80 mm Hg,1 mm Hg=0. 133kPa),AWR score was all significantly higher in FH/Wjd rats than that of SD rats (t=-2. 697,-3.464,-6.822 and -3. 976,P=0. 022,0.006,0.000 and 0.003). The expression level of 5-HT in FH/Wjd rats' control group was significantly higher than that of SD rats' control group (t=-11.371,P=0. 000). Compared with their own control group,5-HT expression increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (t= -3. 364,P= 0. 007). There was no significant difference of c-fos expression in colon and prefrontal brain areas between FH/Wjd rats' control group and SD rats'control group (colon:t=-0. 129,P= 0. 900;IL:t=-1. 316,P= 0. 218;PrL:t=1. 241,P = 0. 243;rACC:t=2. 151,P = 0. 057). Compared with their own control group,the expression of c-fos in colon and prefrontal brain areas significantly increased both in FH/Wjd rats dilated groups and SD rats dilated groups,and the expression level in FH/Wjd rats was higher than that of SD rats (colon: t=- 5.864,P= 0.000;IL:t=-2. 530,P = 0. 030;PrL:t=-7. 039,P= 0. 000;rACC:t=-6. 489,P=0. 000). Conclusions Inherent depressive FH/Wjd rats present visceral hypersensitivity. Meanwhile,the expression of 5-HT in colon is high,and with hyperreactivity to visceral noxious stimuli in colon and brain IL,PrL,and rACC areas. FH/Wjd rats might be a comorbidity animal model of mental disorder and IBS.