【摘要】：背景：脊髓損傷導(dǎo)致了一系列嚴(yán)重的并發(fā)癥,包括癱瘓、疼痛以及進(jìn)行性的神經(jīng)功能障礙等。這不僅對(duì)患者本人的身心是一個(gè)巨大的打擊,也為社會(huì)增加了沉重的經(jīng)濟(jì)負(fù)擔(dān)�；A(chǔ)研究、病例報(bào)道和臨床試驗(yàn)都表明早期治療可以改善神經(jīng)功能的恢復(fù)。但迄今為止,還沒(méi)有成熟的治療方法能夠?qū)ι窠?jīng)學(xué)的結(jié)果產(chǎn)生直接的治療作用,因此需要我們不斷的探索新的治療手段。近年來(lái)很多基礎(chǔ)科學(xué)、實(shí)驗(yàn)研究和臨床研究都致力于防止繼發(fā)性損傷,促進(jìn)再生。這些研究為我們更好的理解脊髓損傷后復(fù)雜病理事件之間的相互聯(lián)系提供了很好的幫助,也為我們未來(lái)的研究指明了方向。目的：探索丹參酮ⅡA對(duì)脊髓損傷大鼠后肢神經(jīng)功能障礙和膀胱功能障礙的影響,并初步探討可能的作用機(jī)制。方法：將64只大鼠隨機(jī)分為四組：對(duì)照組(僅切除椎板,尾靜脈注射生理鹽水1ml/d,連續(xù)7天),模型組(使用NYU Impactor脊髓打擊器選擇25mm高度造成T9脊髓節(jié)段不完全損傷動(dòng)物模型,術(shù)后予尾靜脈注射生理鹽水1ml/d,連續(xù)7天),丹參酮ⅡA組(造模成功后即刻予尾靜脈注射丹參酮ⅡA磺酸鈉注射液2Omg/Kg/d,連續(xù)給藥7天),甲強(qiáng)龍組(造模成功后即刻予尾靜脈注射甲基強(qiáng)的松龍30mg/Kg)。(1)采用BBB評(píng)分法評(píng)價(jià)各組大鼠后肢運(yùn)動(dòng)功能的恢復(fù)；(2)通過(guò)熱板實(shí)驗(yàn)評(píng)價(jià)各組大鼠后肢感覺(jué)功能的恢復(fù)；(3)在術(shù)后7天、4周、8周時(shí)進(jìn)行心臟灌注固定,取材T9脊髓和L6-S1背根神經(jīng)節(jié)；通過(guò)HE染色、尼氏染色觀察脊髓、L6-S1背根神經(jīng)節(jié)局部組織結(jié)構(gòu)的變化,并使用Ⅰ：mage-Pro Plus 6.0病理分析軟件測(cè)量背根神經(jīng)節(jié)細(xì)胞橫截面的面積；(4)術(shù)后4周取材膀胱組織,通過(guò)Masson染色膀胱壁后觀察組織結(jié)構(gòu)的病理變化；(5)術(shù)后7天、術(shù)后8周通過(guò)免疫組化法標(biāo)記各組脊髓中的巨噬/小膠質(zhì)細(xì)胞；(6)術(shù)后4周通過(guò)尿動(dòng)力學(xué)評(píng)價(jià)各組大鼠的膀胱功能。結(jié)果：(1)丹參酮ⅡA組和甲強(qiáng)龍組大鼠后肢運(yùn)動(dòng)功能都有顯著改善,但甲強(qiáng)龍組改善更明顯(P0.05)；(2)術(shù)后3天,甲強(qiáng)龍組感覺(jué)功能恢復(fù)較丹參酮ⅡA組快,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；術(shù)后7天,丹參酮ⅡA組和甲強(qiáng)龍組感覺(jué)功能恢復(fù)程度接近；自術(shù)后2周開(kāi)始,丹參酮ⅡA組表現(xiàn)出了比甲強(qiáng)龍組更明顯的改善趨勢(shì),但并未達(dá)到統(tǒng)計(jì)學(xué)差異(P0.05)。(3)術(shù)后3天,除對(duì)照組,余各組部分巨噬/小膠質(zhì)細(xì)胞形態(tài)由分支狀變?yōu)闂U狀或圓狀,其中丹參酮ⅡA組和甲強(qiáng)龍組形態(tài)改變的細(xì)胞較少,數(shù)量較模型組明顯減少；(4)術(shù)后4周,除對(duì)照組,余各組巨噬/小膠質(zhì)細(xì)胞形態(tài)大部分轉(zhuǎn)變?yōu)榉种?其中模型組大鼠細(xì)胞數(shù)量較對(duì)照組明顯減少,丹參酮ⅡA組細(xì)胞數(shù)量較模型組顯著增加,而甲強(qiáng)龍組細(xì)胞數(shù)量較模型組增加更為明顯。結(jié)論：(1)丹參酮IIA能夠促進(jìn)脊髓損傷大鼠后肢運(yùn)動(dòng)、感覺(jué)功能恢復(fù)；(2)丹參酮IIA能夠改善脊髓損傷后脊髓、膀胱、神經(jīng)節(jié)的病理進(jìn)展,促進(jìn)巨噬/小膠質(zhì)細(xì)胞對(duì)神經(jīng)恢復(fù)的有利影響；(3)丹參酮IIA能夠提高慢性脊髓損傷大鼠排尿效率,減少無(wú)排尿性收縮,促進(jìn)下尿路功能障礙的恢復(fù)；(4)尿動(dòng)力學(xué)是評(píng)價(jià)大鼠下尿路功能的有效手段。
[Abstract]:Background: Spinal cord injury has resulted in a series of serious complications, including paralysis, pain, and progressive neurological dysfunction. This is not only a great blow to the body and mind of the patient, but also a heavy economic burden for society. Basic studies, case reports, and clinical trials have shown that early treatment can improve the recovery of neurological function. But to date, there is no mature method of treatment that can have a direct therapeutic effect on the neurological outcome, so we need to continue to explore new treatments. In recent years, many basic science, experimental research and clinical research work to prevent secondary injury and promote regeneration. These studies provide a good help for our better understanding of the interconnectedness of complex and pathological events after spinal cord injury, as well as directions for our future studies. Objective: To explore the effect of Tanshinone 鈪 on the neurological and bladder dysfunction in the hindlimb of rats with spinal cord injury, and to explore the possible mechanism of action. Methods: Sixty-four rats were randomly divided into four groups: the control group (only the lamina was cut off, the tail vein was injected with normal saline for 1 ml/ d for 7 days), and the model group (using the NYU Impactor's spinal cord) to select the 25 mm height did not completely damage the animal model of the T9 spinal cord. After the operation,1 ml/ d of the normal saline (1 ml/ d,7 days for 7 days) was given, and the tanshinone 鈪 group (the injection of the tanshinone 鈪 sodium sulfonate injection was 2 Omg/ Kg/ d for 7 days after the model was successfully established), and the group A (30 mg/ Kg of methylprednisolone was given to the tail immediately after the model was successfully established). (1) The recovery of the hind limb movement function of each group was evaluated by the BBB scoring method; (2) the recovery of the sensory function of the hind limb of each group was evaluated by a hot plate experiment; (3) the cardiac perfusion was carried out at 7,4 and 8 weeks after the operation, and the spinal cord and the L6-S1 dorsal root ganglion were obtained. The changes of the local tissue structure of the dorsal root ganglion of the spinal cord and the L6-S1 dorsal root ganglion were observed by HE staining, and the area of the cross-section of the dorsal root ganglion cells was measured by using the I: mage-Pro Plus 6.0 pathology analysis software. (4) The bladder tissue was obtained at 4 weeks after operation. The pathological changes of the tissue structure were observed following the staining of the bladder wall by Masson; (5) the macrophagocytic/ microglial cells in each group of the spinal cord were labeled by immunohistochemistry in 7 days after the operation; and (6) the bladder function of each group was evaluated by urodynamics at 4 weeks after operation. Results: (1) There was a significant improvement in the exercise function of the hind limbs of the group A and the group A of the group A, but the improvement of the group A was more obvious (P0.05); (2) The sensory function of the group A was faster than that of the tanshinone 鈪 group after 3 days of operation (P0.05); and after the operation for 7 days, The degree of recovery of the sensory function of the tanshinone 鈪 group and the group A of the group A was close to that of the group A. From the second week after the operation, the group A of the tanshinone 鈪 showed a more obvious improvement tendency than that of the group A, but did not reach the statistical difference (P0.05). (3) After 3 days of operation, in addition to the control group, the morphology of the macrophagocytic/ microglial cells in each group was changed into a rod shape or a round shape, and the number of cells of the tanshinone 鈪 group and the group A of the group A was less and the number of the group was significantly decreased; and (4)4 weeks after the operation, the control group was removed. In the model group, the number of cells in the model group was significantly decreased, and the number of cells in the group A was significantly increased compared with that of the control group, while the number of cells in the group A was more obvious than that of the model group. Conclusion: (1) Tanshinone IIA can promote the hind limb movement and sensory function recovery of spinal cord injury; (2) Tanshinone IIA can improve the pathological progress of spinal cord, bladder and ganglion after spinal cord injury, and promote the beneficial effect of macrophagocyte/ microglial cell on nerve recovery; (3) Tanshinone IIA can improve the micturition efficiency of rats with chronic spinal cord injury, reduce the contractility and promote the recovery of lower urinary tract dysfunction; and (4) the urodynamics is an effective means to evaluate the function of lower urinary tract in rats.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R651.2

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