Sitagliptin对大鼠肢体缺血再灌注损伤的保护作用

Protective effect of Sitagliptin on limb ischemia-reperfusion injury in rats

目的研究磷酸西格列汀(Sitagliptin)对大鼠肢体缺血再灌注损伤的保护作用。方法 8周龄健康清洁级SD大鼠30只,随机分为假手术组(S组)、肢体缺血再灌注组(IR组)、Sitagliptin治疗组(SIR组),各10只。实验前给SIR组的SD大鼠喂养Sitagliptin, 600 mg/(kg·d),共3 d。采用环扎双后肢近心端4 h后再灌注4 h的方法建立大鼠肢体缺血再灌注损伤模型。S组仅麻醉,不阻断后肢血供, 8 h后处死取骨骼肌(腓肠肌)标本。IR组和SIR组,建立大鼠肢体缺血再灌注损伤模型,缺血4 h后再灌注4 h,然后处死大鼠取腓肠肌标本。腓肠肌标本通过HE染色观察腓肠肌组织。另取腓肠肌标本保持冰浴匀浆,取上清液进行测定丙二醛(MDA)及超氧化物歧化酶(SOD)的活性。结果腓肠肌组织切片HE染色显微镜下观察,发现S组大鼠腓肠肌组织细胞排列规则有序,肌纤维连续无断裂。IR组大鼠腓肠肌组织结构紊乱,横纹不清,出现断裂,上述改变在SIR组得到好转。S组SOD活性为(90.72±6.16)U/ml,MDA水平为(41.90±11.18)nmol/(mg·prot);IR组SOD活性为(61.04±5.37)U/ml, MDA水平为(82.25±13.39)nmol/(mg·prot);SIR组SOD活性为(70.87±6.23)U/ml, MDA水平为(68.31±14.95)nmol/(mg·prot)。IR组及SIR组MDA水平高于S组, SOD活性低于S组;SIR组MDA水平低于IR组, SOD活性高于IR组,差异均具有统计学意义(P<0.05)。结论 Sitagliptin能减轻腓肠肌缺血再灌注损伤大鼠腓肠肌组织病变,降低大鼠肢体缺血再灌注损伤组织内MDA的活性、增加SOD的活性,对肢体缺血再灌注损伤大鼠的骨骼肌具有保护作用。

Objective To study the protective effect of Sitagliptin on limb ischemia-reperfusion injury in rats. Methods A total of 30 healthy and clean SD rats at 8 weeks of age were randomly divided into sham operation group(S group), limb ischemia-reperfusion group(IR group), Sitagliptin treatment group(SIR group), with 10 rats in each group. SD rats in SIR group were fed Sitagliptin for 3 d, 600 mg/(kg·d). The rat model of limb ischemia-reperfusion injury was established by ligating the proximal end of both hind limbs for 4 h and then reperfusion for 4 h. S group was anesthetized without blocking the blood supply of hind limbs, and the rats were killed and their skeletal muscles(gastrocnemius) were taken 8 h later. In IR group and SIR group, the rat limb ischemia-reperfusion injury model was established, and after 4 h of ischemia and 4 h of reperfusion, the gastrocnemius muscle samples were taken from the rats. Gastrocnemius tissues were observed by HE staining. In addition, the muscle samples were kept in ice bath homogenate, and the supernatant was taken to measure the activities of malondialdehyde(MDA) and superoxide dismutase(SOD). Results Gastrocnemius muscle sections were observed under microscope after HE staining and found that the gastrocnemius tissue cells of S group were arranged regularly and the muscle fibers were continuous without breakage. In the IR group, the gastrocnemius muscles were structurally disordered, with unclear stripes and fractures, and these changes were improved in SIR group. SOD activity and MDA level of S group were(90.72±6.16) U/ml,(41.90±11.18) nmol/(mg·prot), which were(61.04±5.37)U/ml,(82.25±13.39) nmol/(mg·prot) in IR group, and(70.87±6.23) U/ml,(68.31± 14.95) nmol/(mg·prot) in SIR group. MDA level of IR and SIR group were higher than that of S group, and SOD activity was lower than that of S group;MDA level of SIR group was lower than that of IR group, and SOD activity was higher than that of IR group. The difference was statistically significant(P<0.05). Conclusion Sitagliptin can reduce the pathological changes of gastrocnemius in rats with ischemia-reperfusion injury, decrease the activity of MDA and increase the activity of SOD in rats with limb ischemia-reperfusion injury, and protect the skeletal muscle of rats with limb ischemia-reperfusion injury.