Effects of penehyclidine hydrochloride postconditioning on hind limb ischemia-reperfution injury in rats / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of penehyclldine hydrochloride postconditioning on hind limb ischemia-reperfusion (I/R) injury in rats. Methods One hundred and forty-four male Wistar rats weighing 220-250 g were randomly divided into 4 groups (n = 36 each) control group (group C), I/R group, ischemic postconditioning group (group IPO) and penehyclidine hydrochloride postconditioning group (group PHPO). Limb ischemia was induced by occlusion of bilateral hind limb for 3 h followed by 24 h reperfusion. In group IPO, the animals were subjected to three cycles of 30 s reperfusion and 30 s ischemia on the proximal part of the hind limb,while in group PHPO, the animals received iv injection of penehyclidine hydrochloride 0.15 mg/kg (in normal saline 1 wl) via the caudal vein immediately after reperfusion. Blood samples from the inferior vena cava were taken for determination of activities of serum LDH and CK and concentrations of TNF-α and IL-10 at O, 1, 3, 6, 12 and 24 h of reperfusion. Then 6 rats were sacrificed at each time point respectively and the quadriceps femoris tissues of the hind limb were removed for determination of MDA content, activities of SOD, MPO, Na+ -K+-ATPase and Ca2 + - Mg2+ -ATPase, and HIF- 1 α expression and microscropic examination. Results Compared with group C, the activities of serum LDH and CK and concentrations of TNF-α and IL-10 were significantly increased, the activities of SOD, Na+-K+-ATPase and Ca2+-Mg2+-ATPase were decreased, MPO activities and MDA content were increased, HIF-1α expression was up-regulated in group I/R, IPO and PHPO (P ＜0.05 or 0.01). Compared with group I/R, the serum activities of serum LDH and CK and TNF-α concentration were significantly decreased, IL- 10concentration was increased, activities of SOD, Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were increased, and MPO activity and MDA content were decreased, HIF-1α expression was down-regulated (P ＜ 0.01), and the pathologic changes was reduced in group IPO and PHPO. Compared with group IPO, the serum LDH activity and TNF-α concentration were significantly decreased, CK activity and IL-10 concentration were increased, activities of SOD and MPO and MDA content were decreased and HIF-1α expression was down-regulated (P ＜ 0.05 or 0.01).Conclusion Penehyclidine hydrochloride postconditioning can reduce hind limb I/R injury in rats, and the mechanism is related to inhibiting inflammatory response and lipid peroxidation, reducing calcium overload and improving cellular energy metabolism.