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BACKGROUND/AIMS: Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. METHODS: One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2–14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. RESULTS: Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. CONCLUSIONS: MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.
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Adult , Animals , Female , Humans , Male , Rats , Hypersensitivity , Irritable Bowel Syndrome , Maternal Deprivation , Obesity , Rats, Sprague-DawleyABSTRACT
Objective To observe the protective effects of nuclear factor (NF) κB inhibitor pyrrolidine dithiocarbamate (PDTC) on chronic mixed reflux esophagitis in rats and its influence on NF-κB/interleukin (IL)-6 signaling pathway.Method A total of 40 healthy male Sprague-Dawley (SD) rats were divided into healthy control group,sham operation group,model control group,omeprazole group and PDTC group with eight rats in each group.Except rats in healthy control group and sham operation group,mixed reflux esophagitis model were established in all the other groups.The rats of healthy control group,sham operation group and model control group were all intraperitoneally injected with 2 mL 0.9％ NaCl,rats of omeprazole group were intraperitoneally injected with omeprazole 20 mg/kg,and rats of PDTC group were intraperitoneally injected with PDTC 100 mg/kg every day.After six weeks,the rats were sacrificed,the morphological changes of esophageal tissues were observed and scored by visual inspection and under light microscope.The serum levels of NF-κB p65 and IL-6 in rats of each group were assessed by enzyme linked immunoassay (ELISA).t test was performed for mean comparison among groups.Results The scores of esophageal mucosa judged by visual inspection of healthy control group,sham operation group,model control group,omeprazole group and PDTC group were 0.000 20.000,0.000±0.000,2.250± 0.707,1.125 ± 0.835 and 1.429± 0.535,respectively.The pathological scores were 0.00020.000,0.000±0.000,2.625±0.518,1.500±0.535,1.429±0.535,respectively.Compared with those of model control group,the scores judged by visual inspection and the pathological scores of healthy control group,sham operation group,omeprazole group and PDTC group were lower,and the differences were statistically significant (t=7.603,7.603,2.909,2.506; t=9.674,9.674,4.277,4.399,all P＜0.05).The serum levels of NF-κB p65 protein of healthy control group,sham operation group,omeprazole group and PDTC group were (68.618±18.450) pg/mL,(77.824±22.228) pg/mL,(106.693±45.312) pg/mL and (103.781± 42.502)pg/mL,respectively; compared with that of model group ((184.882±49.165) pg/mL),which were significantly lower and the differences were statistically significant (t=6.262,5.612,3.308 and 3.427,all P＜0.05).The serum levels of IL-6 protein were (24.826±4.008) pg/mL,(23.599±4.351) pg/mL,(32.370± 11.657) pg/mL and (33.694±10.394) pg/mL,respectively,which significantly decreased when compared with that of model group ((51.378±9.697) pg/mL,t=7.157,7.393,3.546 and 3.392,all P＜0.05).There was no significant difference between PDTC group and omeprazole group in the score judged by visual inspection,pathological scores,the serum levels of NF-κB p65 and IL-6 protein (all P＞0.05).Conclusion NF-κB inhibitor PDTC could reduce the injury severity of esophageal mucosal in reflux esophagitis rat,which mechanism might be related with the down-regulation of NF-κB/1L-6 signaling pathway.
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Objective To observe the protective effects of quercetin on esophageal mucosa in chronic mixed reflux esophagitis (RE) rats and the effect of quercetin on nuclear factor (NF)-κB/interleukin (IL)-6 signaling pathway.Methods Mixed RE model was successfully induced by cardia ligation and esophagoduodenostomy.48 healthy male Sprague-Dawley rats were equally divided into the following 6 groups using random number table method:normal control group,sham-operation group,model control group,omeprazole group,low-dose quercetin group,and high-dose quercetin group.The 6 groups were treated with peritoneal injection of 2 ml normal saline (normal control,sham-operation,model control groups),20 mg/kg omeprazole,100 mg/kg quercetin (low-dose) and 200 mg/kg quercetin (high-dose) once daily,respectively.The rats were sacrificed after 6 weeks of intervention.The microscopic pathological changes of esophageal mucosa were scored.NF-κB p65 and IL-6 protein levels in esophageal mucosa and serum were assessed using immunohistochemistry and enzyme-linked immunosorbent assay,respectively.Results In normal control group,shamoperation group,model control group,omeprazole group,low-dose quercetin group and high-dose quercetin group,the pathological scores of esophageal mucosa were 0.250 ± 0.463,0.250 ± 0.463,2.625 ± 0.518,1.500 ±0.535,1.250 ±0.463,and 1.375 ±0.518; the NF-κB p65 protein scores in esophageal mucosa were 0.500±0.535,0.625 ±0.518,3.500 ±0.535,1.875 ±0.649,1.750 ±0.707,and 2.000 ±0.535; the IL-6 protein scores in esophageal mucosa were 1.125 ± 0.641,1.125 ± 0.835,5.375 ± 0.518,2.375 ± 0.518,2.000 ±0.535,and 2.250 ±0.463; the serum NF-κB p65 protein levels were (68.618 ± 18.500),(77.824 ± 22.228),(184.882 ± 49.165),(106.693 ± 45.312),(76.215 ± 16.588),and (108.207 ± 42.107) pg/ml; the serum IL-6 protein levels were (24.826 ±4.008),(23.599 ±4.351),(51.378 ± 9.697),(32.370 ± 11.657),(23.085 ± 4.660),and (26.243 ± 4.955) pg/ml.In terms of the 5 indicators,there were no statistically significant differences between the normal control group and the sham-operation group (P =1.000,P =0.642,P =1.000,P =0.518,P =0.673) ; the results in the normal control,shamoperation,omeprazole,low-dose quercetin,and high-dose quercetin groups were significantly different from those in the model control group (P < 0.001,P < 0.001,P < 0.001,P =0.002,P =0.001 ; P < 0.001,P < 0.001,P<0.001,P=0.004,P=0.002; P=0.001,P<0.001,P<0.001,P=0.025,P=0.023; all P <0.001 ; P <0.001,P <0.001,P <0.001,P =0.023,P <0.001) ; there were no statistically significant differences between low-dose quercetin group and omeprazole group,nor between high-dose quercetin group and omeprazole group (P=0.334,P=0.717,P=0.176,P=0.121,P =0.074; P =0.642,P=0.678,P=0.619,P =0.949,P =0.225); there were no statistically significant differences between low-dose quercetin group and high-dose quercetin group (P =0.619,P =0.438,P =0.334,P =0.086,P =0.243).The microscopic pathological score of esophageal mucosa was positively correlated with NF-κB p65 and IL-6 protein scores in esophageal mucosa (r =0.803,P < 0.001 ; r =0.758,P < 0.001),also positively correlated with serum NF-κB p65 and IL-6 protein levels (r=0.486,P=0.004; r=0.544,P=0.001).Conclusions The expression levels of NF-κB p65 and IL-6 protein in esophageal mucosa and serum increase with the severity of esophageal mucosal injury.Quercetin can reduce the severity of esophageal mucosal injury in RE,possibly through down-regulating NF-κB and IL-6 expression and mitigatng esophageal inflammatory status.
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Objective: To study the protective effect of Complex EGb(C-EGb) on cerebral ischemic damage. Methods: SD rat model of middle cerebral artery occlusion(MCAO) was established according to the method described by Zea Longa,et al. The neurological symptoms and brain infarction range in rat models were evaluated. Mouse model of cerebral ischemia-reperfusion was set up by ligating bilateral common carotid arteries and loosening them in 30 minutes. Effects of C-Egb on superoxide dismutase (SOD) activity, blood glutathione peroxidase (GSH-Px) level, catalase activity and plasma malonyl dialdehyde (MDA) content were observed. Results: C-EGb markedly improved the neurological symptoms and reduced the range of cerebral infarction in MCAO rats. It also decreased the inhibition of SOD, GSH-Px and CAT activity and reduced the production of MDA in ischemia-reperfusion mice. Conclusion: C-EGb has protective effect on brain tissue from cerebral ischemic damage and its effect is better than that of EGb and that of the mixture of EGb.