Intervention And Mechanism Of Flavonoids From Huyou Peel On Intestinal Mucosal Injury Of NSAIDs

Objective To establish a NSAIDs enteropathy model in SD rats,and study the effects of Ghrelin,GHS-R,Leptin,TNF-α on intestinal damage by NSAIDs.Then to explore whether the intervention effect exist of Huyou peel flavonoids on intestinal mucosa of NSAIDs and its possible mechanism of action.Methods Twenty-four male Sprague-Dawley rats were randomly divided into blank group,NSAIDs enteropathy model group and Huyou peel flavonoids treatment group,with 8 rats in each group.The rat model was prepared by pipetting 15 mg/(kg·d)of diclofenac for 5 days.Then drug intervention group was treated with Huyou peel flavonoids 100 mg/(kg·d)for 5 days.At the same time,the blank group and model group were administered with the same dose of normal salineat 6th-10th day.After fasting for 1 day,all rats were sacrificed on the 11th day.Gross lesions of the small intestinal mucosa were measured,histological lesions and intestinal mucosa thickness was measured by HE staining,and the expression of Ghrelin,GHS-R,Leptin and TNF-α were detected by immunohistochemistry.Results Results Compared with the blank group(rat weight gain:67.11±9.45(g),gross score:0.00±0.00,histological score:0.00±0.00,intestinal mucosa thickness:587.45±10.09(um),Ghrelin:12.24 ± 7.44,GHS-R:13.81±6.39,Leptin:8.20±3.98,TNF-α:12.68 ± 2.02),the weight gain of the model group rats(52.31±5.37)(g)was significantly reduced(p<0.05),and the general score(3.50 ± 1.69)and academic score(2.38 ± 1.19)increased(p<0.05),intestinal mucosa thickness(470.46 ± 14.47)(um)thinned(p<0.05),Ghrelin(3.36±1.77),and GHS-R(4.30±1.72)decreased expression(p<0.05),increased expression of Leptin(16.33±4.91)and TNF-α(18.65±2.65)(p<0.05),compared with the model group,the weight gain of rats in the treatment group(61.91± 9.03)(g)markedly increased(p<0.05),gross score(1.50 ± 0.93)and histological score(0.38 ± 0.74)decreased(p<0.05),intestinal mucosa thickness(551.65±10.36)(um)(P<0.05),Ghrelin(7.08 ± 3.04)and GHS-R(11.13±2.71)were up-regulated(p<0.05),Leptin(9.56±3.98)and TNF-α(13.27±2.97)were down-regulated p<0.05).Conclusion Flavonoids of Huyou peel has protective effects on NSAIDs-related small intestinal injury.It can repair the damaged small intestinal mucosa and improve the wasting state of rats.It may work through repairing intestinal mechanical barrier by increasingGhrelin and GHS-R,decreasing Leptin and TNF-α.