【摘要】：目的評(píng)價(jià)青藤堿對(duì)神經(jīng)病理性疼痛的療效以及青藤堿對(duì)神經(jīng)病理性痛大鼠脊髓背角神經(jīng)元凋亡和脊髓氧化應(yīng)激的影響,并探討氧化應(yīng)激在神經(jīng)元凋亡中的作用,研究青藤堿的鎮(zhèn)痛機(jī)制是否通過抑制脊髓的氧化應(yīng)激和脊髓背角神經(jīng)元凋亡而起作用的。方法 由蘭州大學(xué)基礎(chǔ)醫(yī)學(xué)院實(shí)驗(yàn)動(dòng)物中心提供鼠齡1.5-2月、200g左右的Wistar大鼠108只,將其隨機(jī)分為3個(gè)實(shí)驗(yàn)組：假手術(shù)組(S組36只)、青藤堿注射液組(SIN組36只)和神經(jīng)病理性痛組(CCI組36只)。S組不制備神經(jīng)痛模型,只游離坐骨神經(jīng)主干,另外兩組大鼠用坐骨神經(jīng)慢性壓榨性損傷法制備Vistar大鼠神經(jīng)病理性痛模型。SIN組腹腔注射青藤堿注射液4()mg/kg,1次/d,注射時(shí)間為術(shù)后大鼠蘇醒后開始注射至處死前1d,S組和CCI組每日腹腔注射等容量(1.6ml/kg)生理鹽水。在術(shù)前1d(TO)、術(shù)后3d(T1)、7d(T2)、14d(T3)時(shí)分別測(cè)定機(jī)械縮足反應(yīng)閾(MWT)和熱縮足潛伏期(TWL),在術(shù)后T1、T2、T3時(shí)分別測(cè)定痛閾后,每組取大鼠12只處死,取L4-6脊髓組織,其中6只大鼠L4-6脊髓組織用TUNEL法檢測(cè)脊髓背角凋亡神經(jīng)元,另外6只大鼠L4-6脊髓組織測(cè)定脊髓MDA含量及SOD活性,采用分光光度法,并進(jìn)行氧化應(yīng)激指標(biāo)(MDA含量及SOD活性)與神經(jīng)元凋亡的相關(guān)性分析。結(jié)果與S組比較,CCI組和SIN組大鼠的MWT值和TWL值于CCI術(shù)后T1-3時(shí)減小,神經(jīng)元凋亡率升高,脊髓組織中MDA含量增多,SOD活性降低(P0.05)；與CCI組比較,SIN組大鼠的MWT值和TWL值于CCI術(shù)后T1-3時(shí)升高,脊髓背角神經(jīng)元凋亡率降低,脊髓組織中MDA含量減少,SOD活性升高(P0.05)；脊髓組織中SOD活性與脊髓背角神經(jīng)元凋亡率呈負(fù)相關(guān)(r=-0.973,p0.01),MDA含量與神經(jīng)元凋亡率呈正相關(guān)(r=0.929,p0.01)。結(jié)論青藤堿可減輕大鼠神經(jīng)病理性痛,青藤堿可減少神經(jīng)病理性疼痛大鼠脊髓背角神經(jīng)元調(diào)亡和抑制其脊髓氧化應(yīng)激反應(yīng),青藤堿的鎮(zhèn)痛機(jī)制可能是通過抑制脊髓氧化應(yīng)激反應(yīng)從而減少脊髓背角神經(jīng)元凋亡起作用的。
[Abstract]:Objective to evaluate the effect of sinomenine on neuropathic pain and the effect of sinomenine on apoptosis of spinal cord dorsal horn neurons and oxidative stress of spinal cord in rats with neuropathic pain, and to explore the role of oxidative stress in neuronal apoptosis. To study whether the analgesic mechanism of sinomenine can inhibit oxidative stress of spinal cord and apoptosis of spinal dorsal horn neurons. Methods one hundred and eight Wistar rats, aged about 1.5 to 2 months, were randomly divided into 3 groups: sham operation group (S group, 36 rats), and sham operation group (group S, 36 rats). Sinomenine injection group (SIN group, 36 rats) and neuropathic pain group (CCI group, 36 rats) did not produce neuralgia model, but only dissociated sciatic nerve trunk. The other two groups of rats were treated with chronic sciatic nerve compression injury to make the neuropathic pain model of Vistar rats. SIN group was injected with sinomenine injection 4 () mg/kg,1 times per day. The injection time was that the rats were injected intraperitoneally with iso-volume (1.6ml/kg) normal saline (1.6ml/kg) 1 day before the rats were killed and the rats in group S and CCI were injected intraperitoneally with iso-volume (1.6ml/kg). Mechanical foot contraction threshold (MWT) and thermal contraction latency (TWL),) were measured at 3 (T1), 7 (T2) and 14 days (T3) after (TO),. 12 rats were killed in each group. The apoptotic neurons in the spinal cord of L4-6 rats were detected by TUNEL method. The content of MDA and the activity of SOD in the spinal cord of the other 6 rats were measured by spectrophotometry. The correlation between oxidative stress index (MDA content and SOD activity) and neuronal apoptosis was analyzed. Results compared with group S, the values of MWT and TWL in CCI group and SIN group decreased at T1-3 after CCI, the rate of neuronal apoptosis increased, the content of MDA in spinal cord increased and the activity of SOD decreased (P0.05). Compared with CCI group, the MWT and TWL values of SIN group increased at T1-3 after CCI, the apoptosis rate of spinal dorsal horn neurons decreased, the content of MDA in spinal cord tissue decreased and the SOD activity increased (P0.05). There was a negative correlation between the activity of SOD and the apoptosis rate of spinal dorsal horn neurons (r ~ (-0.973) P _ (0.01), MDA) and the apoptotic rate of neurons (r ~ (0.929) P _ (0.01). Conclusion sinomenine can relieve neuropathic pain in rats and sinomenine can reduce the apoptosis of spinal dorsal horn neurons and inhibit the oxidative stress response of spinal cord in rats with neuropathic pain. The analgesic mechanism of sinomenine may reduce the apoptosis of spinal dorsal horn neurons by inhibiting oxidative stress in spinal cord.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R243.2

【共引文獻(xiàn)】

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