ABSTRACT
Objective To approach the effect on mechanical barricade of the mucous membrane of small intestine caused by non-steroidal anti-inflammatory drugs(NSAIDs).Methods Thirty-two male SD rats were randomly divided into control group and model group.The rats of the model group were given 7.5 mg/kg diclofenac by gavage,bid;the rats of the control group were given the same dose of saline.Then thev were further randomly divided into two subgroups(n=8)at the first day and the fifth day after making the models to observe the scores of anatomical lesion on stomach and small intestine and the scores of tissue damage of mucous membrane and to quantitatively analyze the height of villi,as well as the thickness and the section area of mucous membrane with Carl Zeiss Imaging Systems.Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission electron microscope.Results The mucous membrane of stomach of the model groups was slightly edematous.There was no difference between the scores of the model groups and control groups.It was seen that the mucous membrane of small intestine of the first day model group presented with erythema,anabrosis and ulcer.The ulcer was distributed along mesentery.The mucous membrane of small intestine of the fifth day model group showed bleeding,perforation and sinus tract formation,and the scores of anatomical lesion was higher than that of the control group(P＜0.05).The scroes of the lesions of the first and fifth day model groups were 3.5 and 5.0.The difference had statistical significance when compared with those of the control groups(the scores were O)(P＜0.05).Cell degeneration and cellular necrosis of epithelial mueosa of small intestine wag also seen in the first day model group.The top of villi was ablated.The height of the pile on jejunum was (126.9±32.0)μm and that on ileum wag(118.6±22.9)μm They were lower than those of the control group(P＜0.05).However there was no difference of the thickness and section area between them,but the thickness and section area showed a tendency of decrease.It was also seen that there were apomorphosis and sphacelism of epithelial cells in the fifth day model group.Some villi were ablated and laminae propna exposed.The height of villi on jejunum[(73.4±25.4)μm]and that on ileum[(109.3±17.6)μm]decreased significantiy.The thickness of mucous membrane[(123.8±51.6)μm and(165.7±37.4)μm]decreased alnd the section area[(2.48±1.01)mm2 and(3.27±0.76)mm2]became smaller(P＜0.05 vs control group).The mucous membrane of the villi on small intestine wag continuous but arranged disorderly.Cytochondriome swelled,endocytoplasmic reticulia expanded with different degrees,intercellular junction widened Dartly.The microviili in the fifth day model group were ablated more obviously and intercellular iunctions were broken and destroyed gravely.Conclusions Diclofenac can cause damage to the function of mucous membrane barricade of small intestine.It could also lead to shortening of the villi,thinning of the mucous membrane,ablation of the microvilli,and widening of the tight intercellular junction as the characteristic morphological change.
ABSTRACT
Objective To observe the dynamic changes of leptin and transforming growth factor (TGF)-β1 in formation of liver fibrosis in rats,and the role of leptin in liver fibrosis.Methods Six rats were served as normal control(0 week)and killed at the beginning of the study.Thirty-two rats were subcutaneously injected with 60%CCl4 to establish fibrotie models.The rats were than sacrificed at 3,6,9 and 12 weeks with eight each.Expressions of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βRⅡmRNA in liver were detected by reverse-transcription polymerase chain reaction(RT-PCR).Expression of Smad3 and Smad7 proteins were determined by Western blot.The expression and loealization of leptin,Ob-Rb and TGF-β1 in liver tissue were detected by immunohistochemistry.Results The expression of leptin mRNA,Ob-Rb mRNA,TGF-β1 mRNA and TGF-βR Ⅱ mRNA in 0 week were 0.43±0.45,0.57±0.21,0.19±0.12 and 0.30±0.22,respectively,and increased to 1.27±0.19,1.70±0.29,1.70±1.00 and 2.14±1.02 at 12 weeks(P＜0.05).At the same times the level of Smad3 increased from 0.44±0.24 at 0 week to 1.75±1.05 at 12 weeks.While the expression of Smad7 was decreased from 1.35±0.12 at 0 week to 0.74±1.21 at 12 weeks(P＜0.05).The expressions of leptin,Ob-Rb and TGF-β1 were increased with the formation of the fibrosis(P＜0.01).Conclusions With the development of liver fibrosis,the expressions of leptin,Ob-Rb mRNA and protein are increased and improved the formation of the fibrosis.Its mechanisms may be correlated with up-regulation of TGF-β1,TGF-βR Ⅱ and Smda3 expressions and down-regulaton of Smad7 expression by leptin.
ABSTRACT
Objective To establish rat model of small intestinal damage by administrating low dose of diclofenac in short-term and to observe the preventive effect on non steroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage by metronidazole and rabeprazole.Methods Sixty-four rats were randomly divided into control,model,metronidazole and rabeprazole groups with 16 each.The rats in four groups were then further separated into acute stage (T1) and subacute stage (T2) groups.The rats were lavaged with metronidazole (50 mg/kg) and rabeprazole (15 mg/kg) before modeling.The rats in control,model,metronidazole and rabeprazole groups were lavaged with 1ml of distilled water, 7.5 mg/kg diclofenac,50 mg/kg of metronidazole plus 7.5mg/kg of diclofenac,15 mg/kg of rabeprazole plus 7.5mg/kg of diclofenac twice a day,respectively.The rats in T1 group were sacrificed on day 1 and T2 group on day 5.Results Administration of diclofenac induced multiple lesions in the small intestine, such as obviously erythema,erosion,ulcer and cystoid expansion.The lesions in T2 of model group was more seriously than that in T1 group(P＜0.05).And the lesions in model group was also more seriously than that in metronidazole and rabeprazole groups (both T1 and T2 groups,P < 0.05).Serum concentration of NO in T1 of model group was obviously lower than that in control group (P＜0.05),but it was higher in T2 of model group compare to the control group (P＜0.05).There were no significant difference among metronidazole,rabeprazole and model groups in serum level of NO (P>0.05). Conclusions The lesions of small intestinal can be induced by administration of diclofenac.The serum level of NO presents a tendency with decrease before increase afterwards.The metronidazole or rabeprazole has preventive effect on small intestinal lesions.