本文選題：1-溴丙烷　切入點：神經(jīng)毒性　出處：《山西醫(yī)科大學》2013年碩士論文　論文類型：學位論文

【摘要】：目的通過建立1-溴丙烷(1-BP)亞急性吸入染毒模型,研究1-BP對大鼠坐骨神經(jīng)的毒性作用,并探尋反映1-BP對機體損害的指標；通過對1-BP暴露后大鼠尿樣進行檢測,尋找特異靈敏的1-BP接觸標志物。 方法 SPF級成年雄性Wistar大鼠48只按體重隨機分為1-BP暴露低劑量組、中劑量組、高劑量組和對照組,每組12只。各組大鼠均置于動式吸入染毒柜內(nèi),分別給予設定劑量的1-BP1250mg/m3、2500mg/m3、5000mg/m3或新鮮空氣,每天8小時,每周5天,連續(xù)4周。染毒以外時間將大鼠置于代謝籠中收集尿樣。實驗期間每三天稱量一次大鼠體重。染毒結(jié)束次日將大鼠稱重并用戊巴比妥鈉麻醉后,用神經(jīng)肌電儀測定大鼠坐骨神經(jīng)的運動和感覺神經(jīng)傳導速度、末端潛伏期及波幅。之后每組取9只大鼠經(jīng)腹主動脈采血處死,進行血常規(guī)和血生化檢查。每組其余3只大鼠灌流固定后對坐骨神經(jīng)進行病理學檢查。采用氣相色譜法對尿中3-溴丙酸進行測定,采用ICP-MS法對尿樣進行總溴測定。 結(jié)果 1.1-BP染毒期間暴露組大鼠逐漸出現(xiàn)食欲減退、活動減少和被毛稀疏凌亂等表現(xiàn)。染毒期間,低、中濃度染毒組大鼠體重呈增長趨勢,但增長幅度小于對照組。高濃度組體重呈下降趨勢,體重絕對值在染毒第1周后開始低于對照組(P0.05)。染毒3周后高濃度組大鼠后肢肌力明顯下降。 2.神經(jīng)電生理檢查：各暴露組大鼠雙側(cè)運動神經(jīng)傳導速度均顯著低于對照組(P0.01),運動神經(jīng)末端潛伏期均較對照組延長(P0.05)。高濃度組雙側(cè)感覺神經(jīng)傳導速度均低于對照組(P0.05或P0.01),感覺神經(jīng)末端潛伏期均較對照組延長(P0.05或P0.01),低、中濃度組感覺神經(jīng)傳導速度與對照組比較差異無統(tǒng)計學意義(P0.05)。各暴露組運動神經(jīng)和感覺神經(jīng)電刺激波幅與對照組相比均未見顯著差異(P0.05)。 3.血常規(guī)檢查：染毒結(jié)束時高濃度組大鼠的紅細胞數(shù)和血紅蛋白量均顯著低于對照組(P0.05),所有染毒組大鼠紅細胞平均體積(MCV)、平均血紅蛋白量(MCH)和平均血小板體積(MPV)均顯著高于對照組(P0.05)。血清生化檢查：暴露組的AST、ALT值均顯著高于對照組(P0.01),TP、IgG含量隨暴露濃度增高而顯著升高,CK、CP、IgM和鈣離子隨暴露濃度升高而呈降低趨勢； 4.病理學檢查顯示高濃度組大鼠坐骨神經(jīng)髓鞘疏松變性、排列雜亂,部分呈現(xiàn)空泡樣變,軸索腫脹、偏移,間隙增寬。 5.尿中1-BP代謝物測定結(jié)果顯示,各暴露組大鼠尿中總溴值均顯著高于對照組。尿中總溴含量隨著暴露時間的延長而逐漸升高,且和暴露濃度成正相關(guān)。尿中3-溴丙酸含量低于使用方法的檢出限值。 結(jié)論 1.1-BP暴露可引起大鼠坐骨神經(jīng)傳導速度的下降和末端潛伏期延長,運動神經(jīng)比感覺神經(jīng)損傷更敏感；還造成坐骨神經(jīng)髓鞘和軸索的病理改變。坐骨神經(jīng)的運動神經(jīng)傳導速度作為1-BP神經(jīng)損傷的早期檢測指標。 2. MCV、MCH、MPV和AST、ALT值的變化對1-BP暴露敏感,且呈現(xiàn)劑量反映關(guān)系,血清中TP、IgG、CK、CP、IgM和鈣離子值也隨1-BP暴露而發(fā)生顯著變化,這些指標具有作為1-BP毒性作用生物標志物的可能性。 3.大鼠尿中總溴含量對1-BP暴露比較敏感,能夠反映1-BP暴露情況,因此,尿中總溴值具有作為職業(yè)性1-BP接觸的生物標志物的可能。
[Abstract]:Objective to establish a subacute inhalation exposure model of 1- bromine propane (1-BP), to study the toxic effects of 1-BP on sciatic nerve of rats, and to explore indicators that reflect the damage of 1-BP to rats, and to find specific and sensitive 1-BP contact markers by detecting urine samples after 1-BP exposure.
Method
SPF grade 48 adult Wistar male rats were randomly divided into 1-BP exposed to low dose group, middle dose group, high dose group and control group, 12 rats in each group. The rats were placed in a dynamic inhalation cabinet, set were given doses of 1-BP1250mg/m32500mg/m35000mg/m3 or fresh air, 8 hours a day, 5 a week day, for 4 weeks. The exposure time will collect samples outside the rats were placed in metabolic cages. During the experiment, every three days weighing a weight of rats. At the end of the next day the rats were weighed and anesthetized with pentobarbital sodium, determination of rat sciatic nerve motor and sensory nerve conduction velocity of nerve EMG. At the end of latency and amplitude. Then 9 rats from each group were sacrificed by abdominal aortic blood biochemical examination, blood routine and blood. The remaining 3 rats in each group rats perfused after pathological examination of the sciatic nerve. The urine by gas chromatography 3- bromine propionic acid was measured and total bromine was measured by ICP-MS method.
Result
1.1-BP exposure during exposure rats gradually diminished appetite, decreased activity and sparse coat messy performance. During the period of infection, low concentration of body weight in rats showed a rising trend, but the growth rate is less than the control group. High concentration group weight decreased, the absolute value of weight in rats after first weeks was lower than that of control group (P0.05). In the high concentration group of rat hindlimb muscle decreased significantly after 3 weeks.
2. electrophysiological examination: the exposure of bilateral motor nerve conduction velocity of rats were significantly lower than the control group (P0.01), motor nerve terminal latency was longer than the control group (P0.05). The high concentration group of bilateral sensory nerve conduction velocity was lower than the control group (P0.05 or P0.01), sensory nerve latency than the control group extended (P0.05 or P0.01), low concentration group, sensory nerve conduction velocity compared with the control group, the difference was not statistically significant (P0.05). The exposure group, motor nerve and sensory nerve stimulation wave amplitude compared with the control group showed no significant difference (P0.05).
3. blood routine examination: at the end of the experiment the number of red blood cells and hemoglobin content in high concentration group rats were significantly lower than the control group (P0.05), red blood cells of all rats were average volume (MCV), mean hemoglobin (MCH) and mean platelet volume (MPV) were significantly higher than the control group (P0.05). Serum biochemical examination: AST exposure group, ALT values were significantly higher than the control group (P0.01), TP, IgG content increased with the exposure concentration increased significantly, CK, CP, IgM and calcium ion concentration increased with the exposure decreased;
4. the pathological examination showed that the myelin sheath of the sciatic nerve was loose and denatured in the high concentration group and was arranged and disorderly. Some of the vacuolar changes were presented, and the axons were swollen, offset, and widened.
5. the 1-BP metabolites in urine showed that the total bromine value of urine in each exposure group was significantly higher than that in the control group. The total bromine content in urine increased gradually with the prolongation of exposure time, and positively correlated with the exposure concentration. The 3- bromine propionic acid content in urine was lower than the detection limit in use.
conclusion
1.1-BP exposure decreased the sciatic nerve conduction velocity and terminal latency, motor nerve is more sensitive than sensory nerve injury; also caused pathological changes of sciatic nerve myelin and axonal. Motor nerve conduction velocity of sciatic nerve as indicators of early detection of 1-BP nerve injury.
2. MCV, MCH, MPV and AST, ALT values were sensitive to 1-BP exposure, and showed a dose-response relationship. TP, IgG, CK, CP, IgM and Ca2 + values in serum also changed significantly with the exposure of the lungs. These indicators have the possibility of being a biomarker of toxic effects.
The total bromine content in 3. urine is more sensitive to 1-BP exposure, which can reflect 1-BP exposure. Therefore, the total bromine value in urine is a potential biomarker for occupational 1-BP exposure.

【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R114

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