臺灣博碩士論文加值系統

本研究主要以豬為模式探討給予不同濃度單劑量的硝酸鉛溶液後，探討鉛在豬隻體內的動力學的特徵與組織病理變化情形。九頭約30-50公斤的試驗豬，隨機分成3組，分別為口服給藥組（50.0 mg Pb/kg與25.0 mg Pb/kg組）和試驗對照組。利用感應耦合電漿質譜儀（ICP-MS）測定血液、尿液及組織檢品中的鉛含量。結果顯示，鉛在豬隻口服後的血液中濃度經時間變化用一室開放模式表示。結果在血液中(0-28天)的尖峰濃度時間（Tmax）與半衰期（t1/2）：在50.0 mg Pb/kg組分別為 4.0 ± 2.1 小時與 259.1 ± 29.2 小時；而25.0 mg Pb/kg組則分別為 12.0 ± 0.0 小時與 461.2 ± 86.8 小時。血液中的最大濃度（Cmax）與水平-時間曲線下面積（AUC0-672）：50.0 mg Pb/kg組分別為 958.0 ± 97.2 μg/L 與 139464.8 ± 15102.5 μg•hr/L；而25.0 mg Pb/kg組則分別為 372.3 ± 10.5 μg/L 與 90367.4 ± 5868.6 μg•hr/L。由此可知：50.0 mg Pb/kg組血液中的尖峰濃度（Tmax）時間與半衰期（t1/2）分別比25.0 mg Pb/kg組短，且具統計上之顯著差異（P<0.05）。而50.0 mg Pb/kg組的血液中的最大濃度（Cmax）與水平-時間曲線下面積（AUC）又明顯的比25.0 mg Pb/kg組高，亦具有統計上之顯著差異（P<0.05）。所以50.0 mg Pb/kg組試驗豬隻對於鉛的吸收率比25.0 mg Pb/kg組明顯的迅速；而鉛從血液中清除率亦顯著比25.0 mg Pb/kg組快。另外尿液(0-72 hr)的排除的尖峰濃度時間（Tmax）與排除半衰期（t1/2）：在50.0 mg Pb/kg組分別為 2.17 ± 0.67 小時與 48.4 ± 11.4 小時；而25.0 mg Pb/kg組則分別為6.83 ± 3.20 小時與 30.5 ± 3.75 小時。所以50.0 mg Pb/kg組尿液中的排除尖峰濃度時間（Tmax）時間比25.0 mg Pb/kg組短，且具統計上之顯著差異（P<0.05）。而50.0 mg Pb/kg組的尿液中的排除半衰期（t1/2）明顯的比25.0 mg Pb/kg組高，亦具有統計上之顯著差異（P<0.05）。由尿液中的數據結果可知：50.0 mg Pb/kg組的排除速率明顯地比25.0 mg Pb/kg組快。而50.0 mg Pb/kg組與25.0 mg Pb/kg組在各組織中的鉛含量亦無明顯差異（P>0.05）；然而卻顯著得高於對照組的各組織中的鉛含量（P<0.05）。在各組織中鉛含量最高的是肋骨；50.0 mg Pb/kg組含量為24.093 ± 3.478 μg/g 與25.0 mg Pb Pb/kg組含量為 20.495 ± 1.679 μg/g。試驗豬隻分別給與硝酸鉛溶液（50.0 mg Pb/kg與25.0 mg Pb/kg）後，組織鉛含量由高而低，依序為肝臟、毛髮、股骨、腎臟、脾臟、肌肉、心臟與肺臟，含量最低的是腦組織。另外由組織病理切片檢查結果顯示：不同濃度單劑量給藥組對組織器官造成一定程度的損害。本研究結果顯示在豬隻試驗中，單劑量給予硝酸鉛溶液的動力學的試驗結果與其他研究中重複餵飼鉛溶液的研究結果相似，因此鉛對動物體內的影響因素，無論是單劑量急性中毒或慢性連續暴露，所造成複雜的動力學關係，需要更進一步的研究探討。

The objectives of this study were to establish the pharmacokinetic characteristics of different single dosage of lead ingestion and pathological change in swine. Nine hybrid pigs, weighing 30-50 kg, were divided randomly into three groups. Animals were orally dosed with Pb(NO3)2 (50.0 mg Pb/kg and 25.0 mg Pb/kg, respectively,) as treatment groups. One group was treated without Pb(NO3)2 as control. The ICP-MS was used to determine the concentration of lead in blood, urine and tissues. The pharmacokinetic parameters were calculated by using WinNolin software. The unpaired-t test was used for statistical comparison. The Tmax and t1/2 in blood (0-28 days) were 4.0 ± 2.1 hr and 259.1 ± 29.2 hr for 50.0 mg Pb/kg group, and 12.0 ± 0.0 hr and 461.2 ± 86.8 hr for 25.0 mg Pb/kg group, respectively. The Cmax and AUC in blood were 958.0 ± 97.2 μg/L and 139464.8 ± 15102.5 μg•hr/L for 50.0 mg Pb/kg group, and 372.3 ± 10.5 μg/L and 90367.4 ± 5868.6 μg•hr/L for 25.0 mg Pb/kg group, respectively. These results indicated that the 50.0 mg Pb/kg group produced shorter in the Tmax and t1/2, and greater in the Cmax and AUC seems to infer that the lead absorption (ie. accumulated in blood) and clearance from blood was quicker than that of 25.0 mg Pb/kg group significantly (P<0.05). The Tmax and t1/2 in urine were 2.17 ± 0.67 hr and 48.4 ± 11.4 hr for 50.0 mg Pb/kg group, and 6.83 ± 3.20 hr and 30.5 ± 3.7 hr for 25.0 mg Pb/kg group, respectively. These results indicated that the 50.0 mg Pb/kg group in urine produced shorter in the Tmax, and higher in the t1/2 seems indicated that the excretion (ie. eliminated via urine) was faster than that of 25.0 mg Pb/kg group significantly (P<0.05). Also there were no significant differences in tissue lead concentration analyzed between 50.0 mg Pb/kg and 25.0 mg Pb/kg group, nonetheless there were significant differences between control group and lead ingested groups (P<0.05). The highest lead concentration among those tissues was in the rib (24.093 ± 3.478 μg/g for 50.0 mg Pb/kg group and 20.495 ± 1.679 μg/g for 25.0 mg Pb/kg group); followed by descending order, the liver, hair, femur, kidney, spleen, muscle, heart, lung and brain of two lead-ingested groups but not in the control. There were lots of lesions in tissues after different single dosages of lead dosed. In conclusion, this study demonstrated that a single oral administration of lead element produced a complex pharmacokinetics resemble to the orally repeated consumption of lead in swine. The possibility of the blood-compartment and the complex pharmacokinetics need further discussion.

目 錄
目錄………………………………………………………………………………i
摘要………………………………………………………………………………I
一 總論…………………………………………………………………………1
（一）含鉛藥物及藥理介紹…………………………………………………3
1中藥……………………………………………………………………3
2西藥……………………………………………………………………4
（二）環境中的鉛污染來源…………………………………………………5
（三）鉛的藥物動力學/毒理作用介紹……………………………………6
（四）血液/尿液或組織中鉛的定量分析方法介紹………………………8
（五）研究動機/目的………………………………………………………9
二 豬血液/尿液中鉛含量及生化的分析研究……………………………………11
三 豬給與硝酸鉛後 鉛的動力學研究……………………………………99
四 豬給與硝酸鉛後 鉛在組織含量之分佈……………………………………121
五 豬給與硝酸鉛後的組織病理變化分析……………………………………132
六 結論…………………………………………………………………………154
七 參考文獻……………………………………………………………………156
附 錄…………………………………………………………………………168
學術著作………………………………………………………………………i

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