Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion.
OBJECTIVE
To investigate the protective effect of penehyclidine hydrochloride post-conditioning in the damage to the barrier function of the small intestinal mucosa caused by limb ischemia-reperfusion (LIR) injury.


METHODS
Male Wistar rats were randomly divided into three groups (36 rats each): the sham-operation group (group S), lower limb ischemia-reperfusion group (group LIR), and penehyclidine hydrochloride post-conditioning group (group PHC). Each group was divided into subgroups (n = 6 in each group) according to ischemic-reperfusion time, i.e. immediately 0 h (T₁), 1 h (T₂), 3 h (T₃), 6 h (T₄), 12 h (T₅), and 24 h (T₆). Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanter for 3 h. In group PHC, 0.15 mg/kg of penehyclidine hydrochloride was injected into the tail vein immediately after 3 h of bilateral hind-limb ischemia. The designated rats were sacrificed at different time-points of reperfusion; diamine oxidase (DAO), superoxide dismutase (SOD) activity, myeloperoxidase (MPO) of small intestinal tissue, plasma endotoxin, DAO, tumor necrosis factor-α (TNF-α), and interleukin (IL)-10 in serum were detected in the rats.


RESULTS
The pathological changes in the small intestine were observed under light microscope. The levels of MPO, endotoxin, serum DAO, and IL-10 at T₁-T₆, and TNF-α level at T₁-T₄ increased in groups LIR and PHC (P < 0.05) compared with those in group S, but tissue DAO and SOD activity at T₁-T₆ decreased (P < 0.05). In group PHC, the tissue DAO and SOD activity at T₂-T₆, and IL-10 at T₂-T₅ increased to higher levels than those in group LIR (P < 0.05); however, the levels of MPO, endotoxin, and DAO in the blood at T₂-T₆, and TNF-α at T₂ and T₄ decreased (P < 0.05).


CONCLUSIONS
Penehyclidine hydrochloride post-conditioning may reduce the permeability of the small intestines after LIR. Its protection mechanisms may be related to inhibiting oxygen free radicals and inflammatory cytokines for organ damage.
Department of Anesthesiology, First Hospital, Lanzhou University, Lanzhou 730000, Gansu Province, China.
Yan
Y
Zhang
Yu-Fang
YF
Leng
Xing
X
Xue
Yue
Y
Zhang
Tao
T
Wang
Yu-Qing
YQ
Kang
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism; D005121:Extremities / Q000473:pathology*; D005609:Free Radicals / Q000737:chemistry; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008853:Microscopy / Q000379:methods; D010100:Oxygen / Q000737:chemistry; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury
D016207:Cytokines; D004731:Endotoxins; D005609:Free Radicals; D011812:Quinuclidines; C486140:penehyclidine; D010100:Oxygen
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