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山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (9): 53-57.doi: 10.6040/j.issn.1671-7554.0.2015.296

• 基础医学 • 上一篇    下一篇

Lipin1过表达对糖尿病大鼠周围神经病变的影响

徐懿1, 庄向华1, 刘元涛1, 孙爱丽1, 李晓博1, 姜冬青1, 张亮1, 徐敏1, 闫姮2, 陈诗鸿1   

  1. 1. 山东大学第二医院 内分泌科, 山东 济南 250033;
    2. 山东大学第二医院 麻醉科, 山东 济南 250033
  • 收稿日期:2015-03-15 出版日期:2015-09-10 发布日期:2015-09-10
  • 通讯作者: 陈诗鸿。E-mail:chenshihong26@163.com E-mail:chenshihong26@163.com
  • 基金资助:
    国家自然科学基金(81070641);山东省科技发展计划(2014GGE27520);中华医学会临床医学科研专项资金(13020230408);山东省中医药科技发展计划(2013-177)

Over expression of lipin1 attenuates diabetic peripheral neuropathy in rats

XU Yi1, ZHUANG Xianghua1, LIU Yuantao1, SUN Aili1, LI Xiaobo1, JIANG Dongqing1, ZHANG Liang1, XU Min1, YAN Heng2, CHEN Shihong1   

  1. 1. Department of Endocrinology, Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Department of Anesthesiology, Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Received:2015-03-15 Online:2015-09-10 Published:2015-09-10
  • Contact: 陈诗鸿。E-mail:chenshihong26@163.com E-mail:chenshihong26@163.com

摘要: 目的 探讨脂素(Lipin1)对糖尿病(DM)大鼠周围神经早期病变的影响。方法 应用高糖高脂饮食结合腹腔注射链脲佐菌素构建2型糖尿病(T2DM)动物模型,36 只8周龄Wistar大鼠,随机分为空载体(LV-control)组、Lipin1过表达(LV-Lipin1)组,正常对照(NC)组。LV-Lipin1、LV-control组分别通过尾静脉注射Lipin1慢病毒载体与空慢病毒载体。8周后观察各组大鼠空腹血糖(FBG)、体质量(BW);测定坐骨神经传导速度(MNCV);观察坐骨神经病理形态学改变;应用免疫组化法测定Lipin1表达。结果 DM大鼠成模后8周时,LV-control组较NC组Lipin1表达减少,且神经纤维直径、密度、面积均减少(P<0.05);LV-Lipin1组神经纤维直径、密度、面积均较LV-control组改善(P<0.05);LV-Lipin1组较LV-control组坐骨神经神经传导速度明显改善(P<0.05)。结论 DM周围神经病变大鼠坐骨神经中Lipin1表达降低,上调Lipin1表达后DM大鼠坐骨神经神经传导速度改善,病理学观察可见神经髓鞘结构和轴突形态的改善。

关键词: 脂素, 周围神经病变, 慢病毒, 糖尿病

Abstract: Objective To investigate the effects of lipin1 on diabetic peripheral neuropathy in rats. Methods Type 2 diabetes mellitus was induced in male Wistar rats which were fed with high fatty and high sugar diet for 8 weeks, followed by streptozotocin (STZ) injection intraperitoneally. And then the models were randomly divided into Lipin1 high expression (LV-Lipin1) group and empty vector (LV-control) group. Another 12 age-matched non-diabetic rats served as controls. Rats in LV-Lipin1 group were transfected with lentiviral vector expressing rat lipin1; rats in LV-control group were transfected with lentiviral empty vector. After two months, fasting blood glucose, body weight and the motor nerve conduction velocity (MNCV) were measured. Histopathological changes of sciatic nerve were analyzed with light microscope and electron microscope; Lipin1 expression was evaluated with immunohistochemistry. Results Two months after diabetes was induced, expression of Lipin1 in sciatic nerves was significantly decreased in the LV-control group compared with control group. The nerve fiber diameter, nerve fiber area and nerve fiber density in LV-control group were also decreased compared with control group. All of the above changes were significantly attenuated in LV-Lipin1 group. Motor nerve conduction velocity (MNCV) of sciatic nerve in LV-Lipin-1 group was significantly improved compared with LV-control group (P<0.05). Conclusion Expression of Lipin1 in sciatic nerve decreases in diabetic peripheral neuropathy rats. Upregulation of Lipin1 expression significantly improves the MNCV and nerve pathological morphology.

Key words: Lipin1, Peripheral neuropathy, Diabetes, Lentivirus

中图分类号: 

  • R587.1
[1] Ko SH, Kwon HS, Yu JM, et al. Comparison of the efficacy and safety of tramadol/acetaminophen combination therapy and gabapentin in the treatment of painful diabetic neuropathy[J]. Diabet Med, 2010, 27(9): 1033-1040.
[2] Péterfy M, Phan J, Xu P, et al. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin[J]. Nat Genet, 2001, 27(1): 121-124.
[3] Nadra K, de Preux Charles AS, Medard JJ, et al. Phosphatidic acid mediates demyelination in Lpin1 mutant mice[J]. Genes Dev, 2008, 22(12): 1647-1661.
[4] 尚画雨, 夏志, 张丹, 等. 8周游泳运动对2型糖尿病大鼠周围神经病变的影响[J]. 中国病理生理杂志, 2014, 30(4): 719-724. SHANG Huayu, XIA Zhi, ZHANG Dan, et al. Influence of 8-week swimming on peripheral neuropathy in type 2 diabetic rats[J]. Chinese Journal of Pathophysiology, 2014, 30(4): 719-724.
[5] Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: update on definitions,diagnostic criteria, estimation of severity, and treatments[J]. Diabetes care, 2010, 33(10): 2285-2293.
[6] Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neuropathy: where are we now and where to go?[J]. Diabetes Investig, 2011, 2(1): 18-32.
[7] 唐胜球, 江青艳, 杨楚芬, 等. Lipin家族研究进展[J]. 遗传, 2010, 32(10): 981-993. TANG Shengqiu, JIANG Qingyan, YANG Chufen, et al. Research and development of Lipin family[J]. Hereditas, 2010, 32(10): 981-993.
[8] Gowri PM, Sengupta S, Bertera S, et al. Lipin1 regulation by estrogen in uterus and liver: implications for diabetes and fertility[J]. Endocrinology, 2007, 148(8): 3685-3693.
[9] Mul JD, Nadra K, Jagalur NB. A hypomorphic mutation in Lipin1 induces progressively improving neuropathy and lipodystrophy in the rat[J]. J Biol Chem, 2011, 286(30): 26781-26793.
[10] Nadra K, de Preux Charles AS, Medard JJ, et al. Phosphatidic acid mediates demyelination in Lpin1 mutant mice[J]. Genes Devel, 2008, 22(12): 1647-1661.
[11] Verheijen MH, Chrast R, Burrola P, et al. Local regulation of fat metabolism in peripheral nerves[J]. Genes Dev, 2003, 17(19): 2450-2464.
[12] 王国凤, 徐宁, 尹冬, 等. 糖尿病周围神经病变的诊断和治疗新进展[J]. 中国全科医学, 2012, 15(15): 1661-1663. WANG Guofeng, XU Ning, YIN Dong, et al. Diagnosis and treatment progress of diabetic peripheral neuropathy[J]. Chinese General Practice, 2012,15(15): 1661-1663.
[13] Ling Q, Liu M, Wu MX, et al. Anti-allodynic and neuroprotective effects of koumine, a benth alkaloid, in a rat model of diabetic neuropathy[J]. Biol Pharm Bull, 2014, 37(5): 858-864.
[14] Reitman ML.The fat and thin of lipin[J]. Cell Metab, 2005, 1(1): 5-6.
[15] van Harmelenm V, Rydén M, Sjölin E, et al. A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression[J]. Lipid Res, 2007, 48(1): 201-206.
[16] Ueta K, Ishihara T, Matsumoto Y, et al. Long-term treatment with the Na+-glucose cotransporter inhibitor T-1095 causes sustained improvement in hyperglycemia and prevents diabetic neuropathy in Goto-Kakizaki Rats[J]. Life Sci, 2005, 76: 2655-2668.
[17] 方萍, 黄佳佳, 侯瑞芳, 等. 严格血糖控制对糖尿病周围神经病变的影响[J]. 中国糖尿病杂志, 2012, 20(1): 31-35. FANG Ping, HUANG Jiajia, HOU Ruifang, et al. Effect of intensive blood glucose control on the progression of diabetic peripheral neuropathy (DPN)[J]. Chinese Journal of Diabetes, 2012, 20(1): 31-35.
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