溫經(jīng)通絡(luò)法外用對(duì)奧沙利鉑所致周圍神經(jīng)毒性模型干預(yù)的研究
發(fā)布時(shí)間：2018-07-25 20:37
【摘要】：腫瘤發(fā)病率逐年增加,臨床上化療藥物的使用日益廣泛,以?shī)W沙利鉑為代表的化療藥物所致的周圍神經(jīng)毒性(Chemotherapy-induced peripheral neurotoxicity, CIPN)成為腫瘤臨床難治并發(fā)癥,該毒性限制了奧沙利鉑治療劑量的提高并降低了患者的生活質(zhì)量。目前奧沙利鉑所致周圍神經(jīng)毒性的發(fā)病機(jī)制尚不清楚,臨床上沒有很好的治療藥物,是目前國(guó)內(nèi)外專家關(guān)注的難題,需要探索有效可行的解決辦法。 目的：擬通過(guò)復(fù)制奧沙利鉑誘導(dǎo)的周圍神經(jīng)毒性大鼠動(dòng)物模型進(jìn)一步探討中醫(yī)溫經(jīng)通絡(luò)法外用對(duì)周圍神經(jīng)毒性的干預(yù)作用；為臨床中醫(yī)藥防治化療周圍神經(jīng)毒性提供有效方法和科學(xué)依據(jù)。 方法：wistar大鼠50只,隨機(jī)均等分為5組即正常對(duì)照組、模型組、中藥低劑量組、中藥中劑量組、中藥高劑量組。模型組和3個(gè)中藥組腹腔注射奧沙利鉑(樂(lè)沙定)3mg/kg,隔天一次,共16次,正常對(duì)照組則腹腔注射等體積5%葡萄糖溶液對(duì)照；從造模第一天起,3個(gè)中藥組用對(duì)應(yīng)濃中藥煎劑浸泡四肢和尾巴,60min/天,直到造模結(jié)束。于第4、8、12、16次注射奧沙利鉑后測(cè)一次行為學(xué)(機(jī)械刺激感覺異常,冷刺激過(guò)敏反應(yīng),熱痛縮足潛伏期),末次行為學(xué)測(cè)試后,戊巴比妥腹腔麻醉測(cè)坐骨神經(jīng)傳導(dǎo)速度,采集腹腔靜脈血離心取血漿檢測(cè)NGF,取血處死后取第4、5腰椎背根神經(jīng)節(jié)、坐骨神經(jīng)及足底皮膚,福爾馬林固定,石蠟包埋,切片,HE染色觀察背根神經(jīng)節(jié)和坐骨神經(jīng)形態(tài)結(jié)構(gòu)變化,免疫組化染色后,用Image Pro-Plus5.0圖像分析軟件對(duì)背根神經(jīng)節(jié)及足底皮膚P物質(zhì)進(jìn)行半定量分析。 結(jié)果：各中藥組和模型組均出現(xiàn)機(jī)械觸誘發(fā)痛反應(yīng),但中藥高劑量組的機(jī)械觸誘發(fā)痛反應(yīng)較模型組動(dòng)物減少(P0.05)；模型組與正常對(duì)照組及各中藥組相比冷縮足次數(shù)出現(xiàn)明顯差異(P0.05)；提示造模成功。模型組和中藥高劑量組的坐骨神經(jīng)傳導(dǎo)速度較正常對(duì)照組的明顯減慢(P0.01,P0.05)；中藥高劑量組的坐骨神經(jīng)傳導(dǎo)速度明顯快于模型組(P0.05),血清神經(jīng)生長(zhǎng)因子含量中藥高劑量組明顯高于模型組(P0.05),各中藥組間沒有明顯差異；中藥高劑量組組神經(jīng)元細(xì)胞核固縮百分?jǐn)?shù)明顯低于模型組,坐骨神經(jīng)結(jié)構(gòu)改變較模型組輕；足底P物質(zhì)表達(dá)模型組明顯增多(P0.01)。 結(jié)論：溫經(jīng)通絡(luò)散能夠明顯緩解周圍神經(jīng)毒疼痛,加快坐骨神經(jīng)傳導(dǎo)速度,能有效降低奧沙利鉑對(duì)坐骨神經(jīng)的損傷。其治療作用可能是通過(guò)保護(hù)神經(jīng)元細(xì)胞,緩解坐骨神經(jīng)損傷,增加血清神經(jīng)因子表達(dá),減少足底皮膚P物質(zhì)表達(dá)實(shí)現(xiàn)的。
[Abstract]:The incidence of cancer is increasing year by year and the use of chemotherapeutic drugs is becoming more and more extensive. The peripheral neurotoxicity caused by oxaliplatin (Chemotherapy-induced peripheral neurotoxicity, CIPN) has become a difficult complication in clinic. This toxicity limits the increase in the dose of oxaliplatin and reduces the quality of life of patients. At present, the pathogenesis of oxaliplatin induced peripheral neurotoxicity is not clear, and there is no good therapeutic drugs in clinic. It is a difficult problem that experts at home and abroad pay attention to, and need to explore effective and feasible solutions. Objective: to explore the effect of warming meridian and dredging collaterals on peripheral nerve toxicity in rats induced by oxaliplatin. To provide effective methods and scientific basis for the prevention and treatment of peripheral neurotoxicity by traditional Chinese medicine. Methods Fifty Wistar rats were randomly divided into 5 groups: normal control group, model group, low dose group, middle dose group and high dose group. The model group and three traditional Chinese medicine groups were intraperitoneally injected with oxaliplatin (3 mg / kg) once every other day for 16 times, while the normal control group was intraperitoneally injected with 5% glucose solution of the same volume. From the first day of making the model, the three groups were soaked in the limbs and tail for 60 min / day with the corresponding concentrated Chinese medicine decoction until the end of the model making. After injection of oxaliplatin on the 4th week, the behavioral changes were measured once (mechanical irritation, cold irritation, hypersensitivity, latent period of foot contraction). After the last behavioral test, intraperitoneal anesthesia of pentobarbital was used to measure the conduction velocity of the sciatic nerve, and the nerve conduction velocities of the sciatic nerve were measured by intraperitoneal anaesthesia of pentobarbital. Blood samples were collected from abdominal venous blood to determine NGF, and the 5th lumbar dorsal root ganglion (DRG), sciatic nerve and plantar skin, formalin fixation, paraffin embedding, and HE staining were used to observe the morphological and structural changes of DRG and sciatic nerve. After immunohistochemical staining, substance P in dorsal root ganglion and plantar skin were semi-quantitatively analyzed by Image Pro-Plus5.0 image analysis software. Results: mechanical tactile induced pain was found in each Chinese medicine group and model group, but the mechanical touch induced pain response in the high dose group was less than that in the model group (P0.05). Compared with the normal control group and the traditional Chinese medicine group, there was a significant difference between the model group and the traditional Chinese medicine group (P0.05), indicating that the model was successful. The conduction velocity of sciatic nerve in the model group and the high dose group was significantly slower than that in the normal control group (P0.01P 0.05). The conduction velocity of sciatic nerve in high dose group of Chinese medicine was significantly faster than that in model group (P0.05), and the content of serum nerve growth factor in high dose group of Chinese medicine was significantly higher than that in model group (P0.05). The percentage of nuclear pyknosis of neurons in the high dose group was significantly lower than that in the model group, the change of sciatic nerve structure was lighter than that in the model group, and the expression of substance P in the plantar of the model group was significantly increased (P0.01). Conclusion: Wenjing Tongluo Powder can obviously relieve the pain of peripheral nerve poison, accelerate the conduction velocity of sciatic nerve, and effectively reduce the injury of oxaliplatin to sciatic nerve. The therapeutic effect may be achieved by protecting neuron cells, relieving sciatic nerve injury, increasing the expression of serum neurofactor and reducing the expression of substance P in plantar skin.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R273
本文編號(hào)：2145012
[Abstract]:The incidence of cancer is increasing year by year and the use of chemotherapeutic drugs is becoming more and more extensive. The peripheral neurotoxicity caused by oxaliplatin (Chemotherapy-induced peripheral neurotoxicity, CIPN) has become a difficult complication in clinic. This toxicity limits the increase in the dose of oxaliplatin and reduces the quality of life of patients. At present, the pathogenesis of oxaliplatin induced peripheral neurotoxicity is not clear, and there is no good therapeutic drugs in clinic. It is a difficult problem that experts at home and abroad pay attention to, and need to explore effective and feasible solutions. Objective: to explore the effect of warming meridian and dredging collaterals on peripheral nerve toxicity in rats induced by oxaliplatin. To provide effective methods and scientific basis for the prevention and treatment of peripheral neurotoxicity by traditional Chinese medicine. Methods Fifty Wistar rats were randomly divided into 5 groups: normal control group, model group, low dose group, middle dose group and high dose group. The model group and three traditional Chinese medicine groups were intraperitoneally injected with oxaliplatin (3 mg / kg) once every other day for 16 times, while the normal control group was intraperitoneally injected with 5% glucose solution of the same volume. From the first day of making the model, the three groups were soaked in the limbs and tail for 60 min / day with the corresponding concentrated Chinese medicine decoction until the end of the model making. After injection of oxaliplatin on the 4th week, the behavioral changes were measured once (mechanical irritation, cold irritation, hypersensitivity, latent period of foot contraction). After the last behavioral test, intraperitoneal anesthesia of pentobarbital was used to measure the conduction velocity of the sciatic nerve, and the nerve conduction velocities of the sciatic nerve were measured by intraperitoneal anaesthesia of pentobarbital. Blood samples were collected from abdominal venous blood to determine NGF, and the 5th lumbar dorsal root ganglion (DRG), sciatic nerve and plantar skin, formalin fixation, paraffin embedding, and HE staining were used to observe the morphological and structural changes of DRG and sciatic nerve. After immunohistochemical staining, substance P in dorsal root ganglion and plantar skin were semi-quantitatively analyzed by Image Pro-Plus5.0 image analysis software. Results: mechanical tactile induced pain was found in each Chinese medicine group and model group, but the mechanical touch induced pain response in the high dose group was less than that in the model group (P0.05). Compared with the normal control group and the traditional Chinese medicine group, there was a significant difference between the model group and the traditional Chinese medicine group (P0.05), indicating that the model was successful. The conduction velocity of sciatic nerve in the model group and the high dose group was significantly slower than that in the normal control group (P0.01P 0.05). The conduction velocity of sciatic nerve in high dose group of Chinese medicine was significantly faster than that in model group (P0.05), and the content of serum nerve growth factor in high dose group of Chinese medicine was significantly higher than that in model group (P0.05). The percentage of nuclear pyknosis of neurons in the high dose group was significantly lower than that in the model group, the change of sciatic nerve structure was lighter than that in the model group, and the expression of substance P in the plantar of the model group was significantly increased (P0.01). Conclusion: Wenjing Tongluo Powder can obviously relieve the pain of peripheral nerve poison, accelerate the conduction velocity of sciatic nerve, and effectively reduce the injury of oxaliplatin to sciatic nerve. The therapeutic effect may be achieved by protecting neuron cells, relieving sciatic nerve injury, increasing the expression of serum neurofactor and reducing the expression of substance P in plantar skin.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R273
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 汪飛;王躍華;;加味黃芪桂枝五物湯防治奧沙利鉑急性周圍神經(jīng)毒性觀察[J];中醫(yī)藥臨床雜志;2012年04期
2 范曾麗;權(quán)秋梅;;淫羊藿的藥理研究進(jìn)展[J];安徽農(nóng)業(yè)科學(xué);2012年17期
3 楊宏麗;;化療所致神經(jīng)毒性的中醫(yī)診療思路[J];浙江中醫(yī)藥大學(xué)學(xué)報(bào);2010年05期
4 婁彥妮;賈立群;鄧海燕;李利亞;李學(xué);萬(wàn)冬桂;;外用通絡(luò)散治療奧沙利珀化療致周圍神經(jīng)毒性的臨床研究[J];北京中醫(yī)藥;2008年04期
5 徐行;蔣太生;王曉慶;朱海明;;丹紅注射液合彌可保治療奧沙利鉑周圍神經(jīng)毒性42例[J];長(zhǎng)春中醫(yī)藥大學(xué)學(xué)報(bào);2010年05期
6 謝靜;周潔;閻麗珠;;癌復(fù)康Ⅰ號(hào)改善奧沙利鉑周圍神經(jīng)毒性的微循環(huán)檢測(cè)[J];長(zhǎng)春中醫(yī)藥大學(xué)學(xué)報(bào);2012年03期
7 唐玉英;;如意金黃膏治療奧沙利鉑化療后周圍神經(jīng)毒性反應(yīng)的效果觀察[J];當(dāng)代護(hù)士(學(xué)術(shù)版);2009年10期
8 流沙;陳亮;蔡紅衛(wèi);陳兵;;糖尿病大鼠血漿和皮膚中P物質(zhì)檢測(cè)及意義[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2006年10期
9 賴義勤;陳乃杰;吳丹紅;陳云鶯;;健脾益腎法預(yù)防奧沙利鉑周圍神經(jīng)毒性27例[J];福建中醫(yī)藥;2009年05期
10 吳燕;許蓓;陳俊英;;溫經(jīng)通絡(luò)方穴位貼敷防治冬季奧沙利鉑化療致神經(jīng)毒性的臨床研究[J];護(hù)士進(jìn)修雜志;2012年08期
，本文編號(hào)：2145012
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