[Effect of non-steroidal anti-inflammatory drugs on small intestinal barrier function in rats].
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 they 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, amaurosis 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 scores 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 0) (P < 0.05). Cell degeneration and cellular necrosis of epithelial mucosa of small intestine was 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) microm and that on ileum was (118.6 +/- 22.9) microm. 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 propria exposed. The height of villi on jejunum [(73.4 +/- 25.4) microm] and that on ileum [(109.3 +/- 17.6) microm] decreased significantly. The thickness of mucous membrane [(123.8 +/- 51.6) microm and (165.7 +/- 37.4) microm] decreased and 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 was continuous but arranged disorderly. Cytochondriome swelled, endocytoplasmic reticulin expanded with different degrees, intercellular junction widened partly. The microvilli in the fifth day model group were ablated more obviously and intercellular junctions 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.
Zhang
Shuo
S
Department of Gastroenterology, the First Affiliated Hospital, Zhejiang Chinese Medicine University, Hangzhou 310006, China.
Lü
Bin
B
Si
Jian-min
JM
Chen
Fang-ming
FM
Meng
Li-na
LN
Wu
Wei-feng
WF
Yu
Lei-min
LM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac