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電針對骨癌痛-嗎啡耐受大鼠藍(lán)斑核μ阿片受體表達(dá)的干預(yù)

發(fā)布時間:2018-05-04 05:07

  本文選題:骨癌痛 + 嗎啡耐受 ; 參考:《中國針灸》2017年05期


【摘要】:目的:觀察電針對骨癌痛-嗎啡耐受(cancer pain and morphine tolerance)大鼠痛行為的影響及部分作用機制。方法:將42只健康雌性SD大鼠完全隨機分為5組:假手術(shù)組(7只)、骨癌痛組(8只)、嗎啡耐受組(9只)、電針組(9只)和假電針組(9只)。假手術(shù)組于左脛骨髓腔內(nèi)注射無菌磷酸鹽緩沖液,其余4組大鼠均于左脛骨髓腔內(nèi)注射MRMT-1乳腺癌細(xì)胞以制備骨癌痛模型。假手術(shù)組及骨癌痛組術(shù)后均不予干預(yù)。嗎啡耐受組、電針組及假電針組于術(shù)后第11d對骨癌痛制備成功大鼠行鹽酸嗎啡注射液腹腔注射,每12h注射1次,連續(xù)注射11d誘導(dǎo)骨癌痛-嗎啡耐受模型。此模型建立后第1d起,嗎啡耐受組每12h(早上9:00,晚上9:00)行嗎啡注射,連續(xù)7d;電針組、假電針組均于早上9:00行嗎啡注射,30min后分別給予電針(2Hz/100Hz)和假電針(僅刺入皮下,破皮即可)治療,穴取雙側(cè)"足三里"和"昆侖",每次30min,每日1次,連續(xù)治療7d。分別于癌細(xì)胞接種前1d,術(shù)后第6d、8d、10d,嗎啡注射第1d、5d、9d、11d的30min后及電針治療第1d、3d、5d、7d的30min后檢測各組大鼠患側(cè)機械縮足閾(paw withdrawal threshold,PWT)的變化。于嗎啡注射第11d,采用HE染色檢測假手術(shù)組、骨癌痛組、嗎啡耐受組大鼠(每組隨機選2只)脛骨組織形態(tài)學(xué)變化;電針治療第7d采用熒光免疫組織化學(xué)法觀察各組大鼠(每組隨機選4只)藍(lán)斑核μ阿片受體(μ-opioid receptor,MOR)陽性細(xì)胞表達(dá)情況。結(jié)果:癌細(xì)胞接種后第10d,28只骨癌痛造模成功大鼠(骨癌痛組8只、嗎啡耐受組8只、電針組6只、假電針組6只)PWT較7只假手術(shù)組大鼠明顯下降(P0.01)。嗎啡注射第1d,嗎啡耐受組、電針組及假電針組大鼠PWT均明顯高于骨癌痛組(均P0.01);嗎啡連續(xù)注射第11d,嗎啡耐受組、電針組、假電針組大鼠PWT與骨癌痛組比較差異均無統(tǒng)計學(xué)意義(均P0.05)。嗎啡注射第11d,骨癌痛組、嗎啡耐受組大鼠脛骨上1/3處均可見癌細(xì)胞致腫塊,且脛骨髓腔內(nèi)布滿MRMT-1癌細(xì)胞;假手術(shù)組大鼠脛骨未見異常變化。電針治療第1d、3d、5d、7d,骨癌痛組、嗎啡耐受組和假電針組大鼠患側(cè)PWT均明顯低于電針組(均P0.01)。電針治療第7d,骨癌痛組、嗎啡耐受組、電針組、假電針組藍(lán)斑核MOR陽性表達(dá)均低于假手術(shù)組(P0.01,P0.05),且骨癌痛組、嗎啡耐受組和假電針組均低于電針組(均P0.01)。結(jié)論:電針可提高骨癌痛-嗎啡耐受大鼠的機械痛閾,改善模型大鼠痛覺異常;該效應(yīng)可能與電針提高大鼠藍(lán)斑核MOR陽性細(xì)胞表達(dá)有關(guān)。
[Abstract]:Objective: to observe the effect and mechanism of electroacupuncture on pain behavior of pain and morphine tolerance rats. Methods: 42 healthy female SD rats were randomly divided into 5 groups: sham operation group (n = 7), bone cancer pain group (n = 8), morphine tolerance group (n = 9), electroacupuncture group (n = 9) and pseudoelectroacupuncture group (n = 9). In sham-operated group, aseptic phosphate buffer solution was injected into the left tibial medullary cavity, and MRMT-1 breast cancer cells were injected into the left tibial medullary cavity in the other four groups to establish the model of bone cancer pain. There was no intervention after operation in the sham operation group and the bone cancer pain group. Rats in morphine tolerance group, electroacupuncture group and pseudoelectroacupuncture group were injected morphine hydrochloride intraperitoneally every 12 hours on the 11th day after operation. The model of pain and morphine tolerance of bone cancer was induced by continuous injection for 11 days. One day after the establishment of the model, morphine was injected into the morphine tolerance group every 12 hours (9: 00 in the morning, 9: 00 in the evening) for 7 consecutive days, while in the electric acupuncture group, the sham electroacupuncture group was given electroacupuncture 2Hz / 100Hz2 and pseudoelectroacupuncture (only subcutaneously) at 9:00 after morphine injection for 30 minutes. For 7 days, both sides of Zusanli and Kunlun were treated once a day for 30 mins. The changes of paw withdrawal thresholdPWTs were detected at 1 day before inoculation of cancer cells, 8 days after operation, 11 days after morphine injection for 5 days and 9 days after treatment with electroacupuncture for 3 days and 5 days and 7 days after 30min. At the 11th day of morphine injection, the histomorphology of tibia was detected by HE staining in sham-operation group, bone cancer pain group and morphine tolerance group (2 rats in each group). On the 7th day of electroacupuncture treatment, the expression of 渭 -opioid receptor (渭 -opioid receptor) positive cells in the locus coeruleus of rats (4 rats in each group) was observed by fluorescence immunohistochemical method. Results: on the 10th day after inoculation of cancer cells, 28 successful models of bone cancer pain were established in 28 rats (8 in bone cancer pain group, 8 in morphine tolerance group, 6 in electroacupuncture group, 6 in sham electroacupuncture group and 6 in sham operation group). The PWT in sham operation group was significantly lower than that in sham operation group (P 0.01). On the 1st day of morphine injection, the PWT of rats in morphine tolerance group, electroacupuncture group and pseudoacupuncture group were significantly higher than those in bone cancer pain group (all P 0.01), morphine tolerance group, electroacupuncture group, morphine tolerance group and electroacupuncture group on the 11th day of continuous morphine injection. There was no significant difference in PWT between sham electroacupuncture group and bone cancer pain group (P 0.05). On the 11th day of morphine injection, tumor cells were found in the bone cancer pain group and morphine tolerance group, and MRMT-1 cancer cells were found in the medullary cavity of the tibia, but there was no abnormal change in the tibia in the sham operation group. The PWT of the affected side of the rats in the pain group, morphine tolerance group and pseudo-electroacupuncture group were significantly lower than that in the electroacupuncture group (all P 0.01). On the 7th day after electroacupuncture treatment, the positive expression of MOR in bone-cancer pain group, morphine tolerance group, electroacupuncture group and pseudo-electroacupuncture group were all lower than that in sham operation group (P 0.01), and the expression of MOR in bone cancer pain group, morphine tolerance group and pseudoelectroacupuncture group were lower than that in electroacupuncture group (all P 0.01). Conclusion: electroacupuncture can increase the mechanical pain threshold of rats with pain and morphine tolerance of bone cancer and ameliorate the abnormal pain perception in the model rats. This effect may be related to the increase of MOR positive cells expression in the nucleus coeruleus of rats.
【作者單位】: 浙江中醫(yī)藥大學(xué)第三臨床醫(yī)學(xué)院針灸神經(jīng)生物學(xué)實驗室;嘉興學(xué)院附屬第一醫(yī)院針灸科;
【基金】:國家自然科學(xué)基金資助項目:81102643 浙江省自然科學(xué)基金資助項目:LY 14H270016,LQ 15H270003,LY 16H270017 中國博士后基金面上項目:2014 M550334 浙江省醫(yī)藥衛(wèi)生科研項目:2014KYA 162
【分類號】:R245

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