本文選題：脊髓損傷 + 褪黑素�。� 參考：《鄭州大學(xué)》2012年碩士論文

【摘要】：研究背景與目的 脊髓損傷(spinal cord injury, SCI)是一種嚴(yán)重而常見的中樞神經(jīng)系統(tǒng)損傷,它多由創(chuàng)傷和疾病等原因所引發(fā),常導(dǎo)致患者出現(xiàn)嚴(yán)重的運動及感覺功能障礙。脊髓原發(fā)機械損傷后會引起一系列級聯(lián)式的病理變化,主要包括了局部微循環(huán)障礙、氧化應(yīng)激、中性粒細(xì)胞侵潤、細(xì)胞壞死和凋亡等,而SCI往往又是全身多發(fā)創(chuàng)傷的一部分,患者病情常常復(fù)雜而嚴(yán)重,這就給治療時藥物的選擇造提出了很高的要求。目前治療SCI療效確切的藥物并不多,且大多都被證實存在嚴(yán)重的副作用,這就促使我們積極尋找新的藥物來治療SCI。過去的許多研究已證實,褪黑素(melatonin, MT)對脊髓損傷有顯著的治療作用,但對其作用機制的研究還不完善。 材料與方法 60只成年雄性Sprague-Dawley (SD)大鼠隨機分為3組：脊髓損傷組(A組)、褪黑素治療組(B組)、假手術(shù)組(Sham組),每組20只。A、B兩組以改良的Allen's weight drop(WD)法(打擊量50gcf)建立脊髓T12水平損傷模型,Sham組僅行椎板切除術(shù)不損傷脊髓。B組于術(shù)后10min按體重腹腔注射100mg/kg的MT,A組則按體重腹腔注射等體積的無水乙醇(MT的溶劑)。術(shù)后12h對各組大鼠進行神經(jīng)功能評分后處死,取血液及脊髓標(biāo)本檢測NGF、MDA、SOD含量及NGF mRNA表達(dá)水平,并從各組中隨機選取8例脊髓標(biāo)本應(yīng)用HE染色法觀察其一般病理變化,,免疫組化SP法觀察其內(nèi)NGF的表達(dá)特點。統(tǒng)計資料采用SPSS17.0統(tǒng)計分析軟件進行處理,計量資料以x±s表示,多組間比較采用單因素方差分析(ANOVA),各組方差具有齊性時,組間兩兩比較采用最小有意義差異t(LSD-t)檢驗,各組方差不齊時,采用Tamhane's T2檢驗。取α=0.05為顯著性檢驗水準(zhǔn)。 結(jié)果 1.術(shù)后12h,大鼠脊髓內(nèi)NGF mRNA表達(dá)水平和血清中NGF含量各組相較,褪黑素治療組最高、脊髓損傷組次之、假手術(shù)組最低,其差異具有統(tǒng)計學(xué)意義(P0.01)： 2.血清中MDA含量比較,脊髓損傷組最高(P0.01)、褪黑素治療組和假手術(shù)組之間的差異不具有統(tǒng)計學(xué)意義(P0.05)； 3.血清中SOD活性從高到低依次為假手術(shù)組、褪黑素治療組、脊髓損傷組,各組差異具有統(tǒng)計學(xué)意義(P0.01)； 4.脊髓損傷及褪黑素治療組大鼠于術(shù)后均出現(xiàn)了嚴(yán)重的下肢神經(jīng)功能障礙,兩組的BBB運動功能評分差異無統(tǒng)計學(xué)意義(P0.05)。 5.病理學(xué)觀察表明,褪黑素可減輕脊髓損傷早期的病理變化并能提高損傷處脊髓前角及其周圍白質(zhì)內(nèi)NGF的表達(dá)水平(P0.01)。 結(jié)論 1.褪黑素可通過提高大鼠體內(nèi)神經(jīng)生長因子的表達(dá)水平和抑制脂質(zhì)過氧化反應(yīng)治療大鼠脊髓損傷。 2.褪黑素可保護大鼠體內(nèi)SOD的活力,間接地抑制脂質(zhì)過氧化反應(yīng)。 3.按體重腹腔注射l00mg/kg的褪黑素,雖可減輕脊髓損傷早期的病理變化但不能改善大鼠后肢的運動功能障礙。
[Abstract]:Research background and purpose Spinal cord injury (cord injury, SCI) is a serious and common injury to the central nervous system. It is caused by trauma and disease and often leads to severe motor and sensory dysfunction. Spinal cord primary mechanical injury may cause a series of cascade pathological changes, including local microcirculation disorder, oxidative stress, neutrophil infiltration, necrosis and apoptosis, etc. SCI is often a part of multiple trauma. The patient's condition is often complex and serious, which puts forward high requirements for drug selection. At present, there are few effective drugs for SCI, and most of them have been proved to have serious side effects, which urges us to actively seek new drugs to treat SCI. Many previous studies have confirmed that melatonin (MTM) has a significant therapeutic effect on spinal cord injury, but the mechanism of its action is not perfect. Materials and methods Sixty adult male Sprague-Dawley rats were randomly divided into three groups: spinal cord injury group (group A), melatonin treatment group (group B) and sham group (group B). Model sham group only underwent laminectomy without spinal cord injury. Group B received intraperitoneal injection of 100mg/kg according to body weight after 10min. The rats in each group were killed 12 hours after operation. The blood and spinal cord specimens were taken to detect the content of NGF mRNA and the content of SOD. Eight cases of spinal cord specimens were randomly selected from each group to observe the general pathological changes by HE staining and immunohistochemical SP method to observe the expression of NGF in the spinal cord. The statistical data were processed by SPSS17.0 statistical analysis software, the measurement data were expressed as x 鹵s, and the single factor analysis of variance (ANOVAN) was used in the multigroup comparison. When the variance of each group was homogeneous, the least significant difference between the two groups was used to test. Tamhane's T2 test was used when the variance of each group was not equal. A 0.05 was taken as the significant test level. Result 1. At 12 hours after operation, the expression of NGF mRNA in spinal cord and the content of NGF in serum of rats were the highest in melatonin treatment group, followed by spinal cord injury group and sham operation group. The difference was statistically significant (P 0.01). 2. The MDA content in serum was the highest in the spinal cord injury group (P 0.01), but there was no significant difference between the melatonin treatment group and the sham operation group (P 0.05). 3. The activities of SOD in serum from high to low were sham-operation group, melatonin treatment group and spinal cord injury group. 4. The rats in spinal cord injury and melatonin treatment group had severe lower extremity neurological dysfunction after operation. There was no significant difference in BBB motor function score between the two groups (P 0.05). 5. Pathological observation showed that melatonin could attenuate the early pathological changes of spinal cord injury and increase the expression level of NGF in the anterior horn of spinal cord and its surrounding white matter. Conclusion 1. Melatonin can improve the expression of nerve growth factor and inhibit lipid peroxidation in the treatment of spinal cord injury in rats. 2. Melatonin can protect the activity of SOD and indirectly inhibit lipid peroxidation in rats. 3. Intraperitoneal injection of melatonin (l00mg/kg) according to body weight could attenuate the early pathological changes of spinal cord injury but could not improve the motor dysfunction of hind limbs in rats.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R651.2;R-332

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