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目的探讨钙蛋白酶抑制剂(calpeptin,CP)对丙烯酰胺(acrylamide,ACR)中毒大鼠神经毒性的拮抗作用。方法将30只健康成年雌性Wistar大鼠随机分为对照组、ACR中毒组、CP干预组3组,每组10只。ACR中毒组腹腔注射ACR30 mg/kg,3次/周,共4周;对照组腹腔注射等体积生理盐水;CP干预组腹腔注射ACR后1 h再腹腔注射CP 200μg/kg,3次/周,共4周。测定体重、步态评分、后肢撑力和神经组织细胞内钙蛋白酶(calpain)活力。结果与对照组相比,ACR中毒组大鼠体重增加缓慢(P<0.05);与ACR中毒组相比,CP干预组大鼠体重在第2周显著升高(P<0.05)。ACR中毒组和CP干预组步态评分和后肢撑力明显高于对照组(P<0.01),CP干预组明显高于ACR组(P<0.05)。ACR中毒组和CP干预组脊髓、坐骨神经细胞中calpain活力均明显高于对照组(CP干预组坐骨神经除外);CP干预组脊髓、坐骨神经细胞中calpain活力明显低于ACR组(P<0.05)。结论 CP可通过抑制钙蛋白酶的活力拮抗ACR诱导的神经毒作用。
Objective To investigate the antagonistic effect of calpeptin (CP) on the neurotoxicity of acrylamide (ACR) intoxication rats. Methods Thirty healthy adult female Wistar rats were randomly divided into control group, ACR poisoning group and CP intervention group, with 10 rats in each group. ACR intoxication group were intraperitoneally injected with ACR30 mg / kg for 3 times / week for 4 weeks. The control group was given intraperitoneal injection of equal volume of normal saline. CP group was intraperitoneally injected with CP 200 μg / kg, A total of 4 weeks. Body weight, gait score, hindlimb bracing, and calpain activity of nerve tissue were measured. Results Compared with the control group, the body weight of rats in ACR poisoning group increased slowly (P <0.05). Compared with ACR poisoning group, the weight of rats in CP intervention group increased significantly at the second week (P <0.05). The scores of gait and hindlimb support in ACR and CP intervention groups were significantly higher than those in control group (P <0.01), and those in CP intervention group were significantly higher than those in ACR group (P <0.05). The activity of calpain in spinal cord and sciatic nerve of ACR poisoning group and CP intervention group were significantly higher than that of control group (except for the sciatic nerve in CP intervention group). The activity of calpain in spinal cord and sciatic nerve of CP group was significantly lower than that of ACR group (P <0.05). Conclusion CP can antagonize ACR-induced neurotoxicity by inhibiting the activity of calpain.