17β-雌二醇對去勢大鼠慢性脊髓損傷后神經保護作用的實驗研究_《中國修復重建外科雜志》

作者：

李延宏 , 楊同群 , 王秉義 , 張謙 , 耿喜林 , 王顥

蘭州大學第二醫院創傷外科（蘭州，730030）;

關鍵詞：

17β-雌二醇慢性脊髓損傷神經保護大鼠

DOI：

10.7507/1002-1892.20130159

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目的探討17β-雌二醇對去勢大鼠慢性脊髓損傷后神經細胞凋亡的影響。方法取90只雌性Wistar大鼠，體重220～250 g，行雙側卵巢切除術；2周后將大鼠隨機分為3組（n=30）：假手術組（A組），慢性漸進性壓迫性脊髓損傷加17β-雌二醇組（B組）、慢性漸進性壓迫性脊髓損傷空白對照組（C組）。A組僅手術切除T10棘突；B、C組制備慢性漸進性壓迫性脊髓損傷模型后，分別于造模后每周腹腔注射17β-雌二醇2次（每次100 μg/kg）和相同劑量生理鹽水。于造模后1、3、7、14、28、60 d采用改良Tarlov評分及斜板實驗評分觀察大鼠運動功能情況，取材后行HE染色、半胱氨酸蛋白酶3（Caspase-3）免疫組織化學染色及TUNEL染色觀察。結果造模后14、28及60 d，B組改良Tarlov評分及斜板實驗評分均優于C組，但低于A組，差異有統計學意義（P lt; 0.05）。HE染色示，造模28 d B組鏡下見脊髓灰質輕度水腫、神經元腫脹，有少量膠質細胞和星形膠質細胞增生，病理改變較C組減輕；60 d B組脊髓灰質輕度水腫、神經元腫脹均明顯減輕。造模后14、28、60 d B組Caspase-3陽性細胞百分率顯著低于C組，7、14、28、60 d B組細胞凋亡率顯著低于C組，但均高于A組，差異均有統計學意義（P lt; 0.05）。結論17β-雌二醇能減少大鼠慢性脊髓損傷后神經細胞凋亡，促進神經功能恢復。

引用本文： 李延宏,楊同群,王秉義,張謙,耿喜林,王顥. 17β-雌二醇對去勢大鼠慢性脊髓損傷后神經保護作用的實驗研究. 中國修復重建外科雜志, 2013, 27(6): 720-725. doi: 10.7507/1002-1892.20130159 復制

1.	Sur P, Sribnick EA, Wingrave JM, et al. Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. Brain Res, 2003, 971(2): 178-188.
2.	Yune TY, Kim SJ, Lee SM, et al. Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma, 2004, 21(3): 293-306.
3.	Schramm J. A model for chronic spinal cord compression in cats. Neurochirurgia (Stuttg), 1982, 25(4): 113-115.
4.	Salzman SK, Puniak MA, Liu ZJ, et al. The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma. Ann Neurol, 1991, 30(4): 533-541.
5.	Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. Neurosurg, 1977, 47(4): 577-581.
6.	Cardona-Rossinyol A, Mir M, Caraballo-Miralles V, et al. Neuroprotective effects of estradiol on motoneurons in a model of rat spinal cord embryonic explants. J Cell Mol Neurobiol, 2013, 33(3): 421-432.
7.	Das A, Smith JA, Gibson C, et al. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol, 2011, 208(2): 171-182.
8.	Sribnick EA, Wingrave JM, Matzelle DD, et al. Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann N Y Acad Sci, 2003, 993: 125-133.
9.	Sribnik EA, Ray SK, Nawak MW, et al. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res, 2004, 76(5): 688-696.
10.	Mermelstein PG. Membrane-localised oestrogen receptor alpha and beta influence neuronal activity through activation of metabotropic glutamate receptors. J Neuroendocrinol, 2009, 21(4): 257-262.
11.	Rong W, Wang J, Liu X, et al. 17β-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci, 2012, 122(7): 381-387.
12.	Kachadroka S, Hall AM, Niedzielko TL, et al. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma, 2010, 27(3): 611-626.
13.	Lee JY, Choi SY, Oh TH, et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. J Endocrinology, 2012, 153(8): 3815-3827.
14.	Siriphorn A, Dunham KA, Chompoopong S, et al. Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol, 2012, 520(12): 2630-2646.
15.	Thompson KE, Sipes IG, Greenstein BD, et al. 17beta-estradiol affords protection against 4-vinylcyclohexenediepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology, 2002, 143(3): 1058-1065.
16.	Khalaj L, Peirovi H, Khodagholi F, et al. Acute 17β-estradiol pretreatment protects against abdominal aortic occlusion induced spinal cord ischemic-reperfusion injury. J Neurochem Res, 2011, 36(2): 268-280.
17.	Maier JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci, 2002, 22(6): 2035-2043.
18.	Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg, 2002, 89(6): 911-920.
19.	Matsushita K, Wu Y, Qiu J, et al. Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci, 2000, 20(18): 6879-6887.
20.	Sribnick EA, Matzelle DD, Ray SK, et al. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res, 2006, 84(5): 1064-1075.

1. Sur P, Sribnick EA, Wingrave JM, et al. Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells. Brain Res, 2003, 971(2): 178-188.
2. Yune TY, Kim SJ, Lee SM, et al. Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma, 2004, 21(3): 293-306.
3. Schramm J. A model for chronic spinal cord compression in cats. Neurochirurgia (Stuttg), 1982, 25(4): 113-115.
4. Salzman SK, Puniak MA, Liu ZJ, et al. The serotonin antagonist mianserin improves functional recovery following experimental spinal trauma. Ann Neurol, 1991, 30(4): 533-541.
5. Rivlin AS, Tator CH. Objective clinical assessment of motor function after experimental spinal cord injury in the rat. Neurosurg, 1977, 47(4): 577-581.
6. Cardona-Rossinyol A, Mir M, Caraballo-Miralles V, et al. Neuroprotective effects of estradiol on motoneurons in a model of rat spinal cord embryonic explants. J Cell Mol Neurobiol, 2013, 33(3): 421-432.
7. Das A, Smith JA, Gibson C, et al. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol, 2011, 208(2): 171-182.
8. Sribnick EA, Wingrave JM, Matzelle DD, et al. Estrogen as a neuroprotective agent in the treatment of spinal cord injury. Ann N Y Acad Sci, 2003, 993: 125-133.
9. Sribnik EA, Ray SK, Nawak MW, et al. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res, 2004, 76(5): 688-696.
10. Mermelstein PG. Membrane-localised oestrogen receptor alpha and beta influence neuronal activity through activation of metabotropic glutamate receptors. J Neuroendocrinol, 2009, 21(4): 257-262.
11. Rong W, Wang J, Liu X, et al. 17β-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci, 2012, 122(7): 381-387.
12. Kachadroka S, Hall AM, Niedzielko TL, et al. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats. J Neurotrauma, 2010, 27(3): 611-626.
13. Lee JY, Choi SY, Oh TH, et al. 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. J Endocrinology, 2012, 153(8): 3815-3827.
14. Siriphorn A, Dunham KA, Chompoopong S, et al. Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. J Comp Neurol, 2012, 520(12): 2630-2646.
15. Thompson KE, Sipes IG, Greenstein BD, et al. 17beta-estradiol affords protection against 4-vinylcyclohexenediepoxide-induced ovarian follicle loss in Fischer-344 rats. Endocrinology, 2002, 143(3): 1058-1065.
16. Khalaj L, Peirovi H, Khodagholi F, et al. Acute 17β-estradiol pretreatment protects against abdominal aortic occlusion induced spinal cord ischemic-reperfusion injury. J Neurochem Res, 2011, 36(2): 268-280.
17. Maier JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7. J Neurosci, 2002, 22(6): 2035-2043.
18. Emery E, Aldana P, Bunge MB, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg, 2002, 89(6): 911-920.
19. Matsushita K, Wu Y, Qiu J, et al. Fas receptor and neuronal cell death after spinal cord ischemia. J Neurosci, 2000, 20(18): 6879-6887.
20. Sribnick EA, Matzelle DD, Ray SK, et al. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. J Neurosci Res, 2006, 84(5): 1064-1075.

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《中國修復重建外科雜志》

17β-雌二醇對去勢大鼠慢性脊髓損傷后神經保護作用的實驗研究

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