中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (5): 942-950.doi: 10.12307/2025.248

• 神经组织构建 nerve tissue construction • 上一篇    下一篇

普伐他汀对大鼠坐骨神经压碎损伤功能恢复的影响

刘  赞1，2，安  冉1，李宝成2   

  1. 1内蒙古科技大学包头医学院，内蒙古自治区包头市  014000；２内蒙古科技大学包头医学院第一附属医院手足踝外科，内蒙古自治区包头市014010


  • 收稿日期:2024-01-10 接受日期:2024-02-22 出版日期:2025-02-18 发布日期:2024-06-03
  • 通讯作者: 李宝成，教授，主任医师，内蒙古科技大学包头医学院第一附属医院手足踝外科，内蒙古自治区包头市 014010
  • 作者简介:刘赞，男，1989年生，河南省泌阳县人，汉族，内蒙古科技大学包头医学院在读硕士，主要从事周围神经损伤修复方面的研究。 并列第一作者：安冉，女，1997年生，山西省晋中市人，汉族，内蒙古科技大学包头医学院在读硕士，主要从事神经外科方面的研究。
  • 基金资助:
    包头医学院研究生科研创新项目(bycx2023013)，项目负责人：安冉

Effect of pravastatin on functional recovery from sciatic nerve crush injury in rats 

Liu Zan1, 2, An Ran1, Li Baocheng2   

  1. 1Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China; 2Department of Hand, Foot and Ankle Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, Inner Mongolia Autonomous Region, China
  • Received:2024-01-10 Accepted:2024-02-22 Online:2025-02-18 Published:2024-06-03
  • Contact: Li Baocheng, Professor, Chief physician, Department of Hand, Foot and Ankle Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, Inner Mongolia Autonomous Region, China
  • About author:Liu Zan, Master candidate, Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou 014000, Inner Mongolia Autonomous Region, China; Department of Hand, Foot and Ankle Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014010, Inner Mongolia Autonomous Region, China An Ran, Master candidate, Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou 014000,Inner Mongolia Autonomous Region, China Liu Zan and An Ran contributed equally to this work.
  • Supported by:
    Graduate Student Research and Innovation Program of Baotou Medical College, No. bycx2023013 (to AR)

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摘要：




文题释义：
普伐他汀：属于竞争性羟甲基戊二酰辅酶A (HMG Co-A)还原酶抑制剂一类，在胆固醇生物合成的限速步骤中发挥抑制作用，是临床上一种用于治疗原发性高胆固醇血症、高脂血症和混合性血脂异常的重要药物，同时它还具有抗炎、抗氧化、免疫调节和神经保护作用。
周围神经损伤：是指除脑和脊髓以外的所有神经受到伤害而发生的损伤，其发病率高，发病原因众多，如感染、缺血、创伤、医源性损伤等，可导致受伤肢体的运动、感觉及自主神经功能障碍。周围神经损伤的治疗手段包括显微外科手术、自体神经移植、异体神经移植、神经引导导管、药物等，部分患者能被治愈，但也有少数患者终身残疾。

背景：普伐他汀是临床上治疗高胆固醇血症的有效药物，目前发现其在中枢神经损伤的治疗上也能发挥有益作用，然而其机制仍未可知。
目的：探究普伐他汀治疗能否加速坐骨神经压碎损伤的功能恢复及其潜在作用机制。
方法：将雄性SD大鼠随机分为假手术组(坐骨神经暴露但不损伤+生理盐水灌胃)、阴性对照组(坐骨神经压碎损伤+生理盐水灌胃)、普伐他汀组(坐骨神经压碎损伤+普伐他汀灌胃)。普伐他汀组大鼠术后普伐他汀(5 mg/kg)灌胃治疗1周，其余两组大鼠给予等量生理盐水灌胃。术后观察各组大鼠一般情况；术后第2，4，6，8周末测量各组大鼠的坐骨功能指数；术后8周末测量腓肠肌湿质量比；ELISA法检测血清中炎症细胞因子的水平；组织形态计量学分析坐骨神经有髓神经纤维数目、纤维直径、轴突直径、髓鞘厚度；RT-qPCR检测神经生长因子、脑源性神经营养因子的mRNA表达量，Western blot法检测生长相关蛋白43的蛋白表达量。
结果与结论：与阴性对照组相比，普伐他汀组坐骨神经功能指数恢复更快(P < 0.05)，更接近于假手术组水平，血清中炎症细胞因子肿瘤坏死因子α及白细胞介素6表达更低(P < 0.05)且接近假手术组，坐骨神经中神经生长因子、脑源性神经营养因子的mRNA相对表达量增加(P < 0.05或P < 0.01)，坐骨神经中生长相关蛋白43的蛋白相对表达量也明显增加(P < 0.05)，有髓神经纤维数目增加更多，纤维直径、轴突直径及髓鞘厚度数值更大(P < 0.01)且与假手术组更接近。结果说明，普伐他汀的治疗加速了坐骨神经压碎损伤的功能恢复，其可能机制是抑制炎症细胞因子肿瘤坏死因子α及白细胞介素6的表达及促进神经营养因子神经生长因子、脑源性神经营养因子的分泌。

https://orcid.org/0009-0000-7354-6213(刘赞)；https://orcid.org/0009-0005-5840-8943(安冉)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 周围神经损伤, 普伐他汀, 功能恢复, 神经营养因子, 坐骨神经功能指数

Abstract: BACKGROUND: Pravastatin is a clinically effective drug for the treatment of hypercholesterolemia and is now found to play a beneficial role in the treatment of CNS injury; however, the mechanism remains unknown.
OBJECTIVE: To ascertain the possible mechanism of action and whether pravastatin medication can expedite functional recovery following sciatic nerve crush injury.
METHODS: Male Sprague-Dawley rats were randomly assigned into: pravastatin (sciatic nerve crush injury+pravastatin gavage), negative control (sciatic nerve crush injury+saline gavage), and sham operation (sciatic nerve exposure but no injury+saline gavage). While the other two groups received comparable amounts of saline gavage, the pravastatin group received postoperative pravastatin (5 mg/kg) by gavage for 1 week. The general conditions of the rats in each group were observed after operation. Sciatic function index was evaluated at the end of the 2nd, 4th, 6th, and 8th week after operation, and the wet mass ratio of the gastrocnemius muscle was measured at the end of the 8th week after operation. The levels of inflammatory cytokines in serum were measured using ELISA. Histomorphometrics was used to measure the number of myelinated nerve fibers, fiber diameter, axon diameter, and myelin sheath thickness. RT-qPCR assay was used to measure the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor, and western blot was used to measure the protein expression of growth-associated protein 43.
RESULTS AND CONCLUSION: Compared with the negative control group, the sciatic function index in the pravastatin group recovered faster (P < 0.05) and was closer to the level of the sham operation group, the expression of tumor necrosis factor α and interleukin 6 in serum was lower (P < 0.05) and close to that of the sham operation group, and the relative mRNA expression of nerve growth factor and brain-derived neurotrophic factor in the sciatic nerve increased (P < 
0.05 or P < 0.01), the relative protein expression of growth-associated protein 43 in the sciatic nerve was also significantly increased (P < 0.05), the number of myelinated nerve fibers was increased more, and the values of fiber diameter, axon diameter, and myelin sheath thickness were larger (P < 0.01) and closer to those of the sham operation group. To conclude, treatment with pravastatin accelerates functional recovery from sciatic nerve crush injury by a possible mechanism of inhibiting the expression of tumor necrosis factor α and interleukin 6 and promoting the secretion of neurotrophic factors nerve growth factor and brain-derived neurotrophic factor.


Key words: peripheral nerve injury, pravastatin, functional recovery, neurotrophic factor, sciatic function index

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