• 沒有找到結果。

緒論

無論鉛是急性或慢性長期暴露,對於生物體都是一種危害,有的危害是 可逆的,有的卻是不可逆,這與各組織受到的鉛含量有相關性[146],但採取 組織樣品進行鉛含量測定,是侵入性之採樣方式,對受採樣者是種傷害,所 以相關樣品之採集相當困難,因此對各組織所受的傷害影響無法立即得知,

只能從小動物[147]或生化檢驗報告中得知。真正可以瞭解急性大量鉛吸收 後,對於體內組織傷害的研究並不多,所以本研究利用生理解剖結構與人類 相似的猪隻,當作試驗動物,於單劑量鉛餵飼後,進行組織採樣,測定各組 織之鉛含量分佈情形,並進行組織病理變化分析,以作為其他相關研究之用。

材料與方法

購自台灣動物科技研究所之 30-50 公斤,健康情況良好之三品種雜交肉 猪 9 頭(母),隨機分成三組,每組各三頭,猪隻於血樣及尿液採樣結束後 三週時,以安樂死(KCl)方式犧牲猪隻,進行組織採樣,分別採取肝、心、

脾、肺、腎與大腦組織各 5-10 公克,並將部分肝、心、脾、肺、腎及大腦 組織浸泡於 10 %中性福馬林溶液中,待固定數日後,供作病理組織切片製 作與檢查[148]。

結果與討論

由表 5-1 可知二試驗組之各組織鉛含量濃度,由高至低排列分別為:肝

臟、腎臟、脾臟、心臟、肺臟、大腦。由表 5-2、5-3 與圖 5-1 至 5-7 得知,

三組間的組織病理切片分析結果如下:對照組除肝臟呈現出輕微門脈周圍纖 維化、三角區炎症反應以及膽管增生之現象與肺臟有局部慢性、多發性間質 性肺炎外,其他各組織無明顯之病理變化。25 mg Pb/kg 組之肝臟則發現有 輕度門脈周圍纖維化、三角區炎症反應以及膽管增生之現象;腎臟組織部分 則有輕度、亞急性之局部淋巴球性間質腎炎,或伴有輕度腎小管再生與輕度 間質性纖維化現象;脾臟則無明顯病理病變;在心臟(心肌)檢查則發現有輕 度局部之淋巴球性心肌炎、心肌纖維化現象或無明顯病理病變;肺臟則有不 同程度之輕中度、慢性瀰漫性之間質肺炎或伴發類淋巴結節樣增生之間質性 或慢性多發性局部肺炎;腦 (大腦)部分則有輕微局部性淋巴球性之血管炎或 伴有急性神經元變性或無明顯病理病變發生。

另外於 50 mg Pb/kg 組之肝臟則同樣發現有輕度門脈周圍纖維化、三角 區炎症反應以及膽管增生,或伴有輕度多發局部性巨大細胞浸潤之現象;腎 臟組織部分則有輕度、亞急性之局部淋巴球性間質腎炎或無明顯病理病變產 生;脾臟則無明顯病理病變;心臟 (心肌) 則有輕度急性,局部多發性鬱血 性心肌病變,或慢性輕度伴有心肌纖維溶解,心肌纖維斷裂之局部性心肌纖 維化產生,或無明顯病理病變;肺臟則有輕度、慢性瀰漫性,或伴有類淋巴 結節樣增生之間質性肺炎,或肺氣腫產生;在腦 (大腦組織方面則發現有輕 微淋巴球性或伴有神經元變性之腦膜炎現象產生。

由以上得知二試驗組各組織的病變顯著地比試驗對照組嚴重,雖然對照 組的肺臟與肝臟有輕微的病變產生,但一般猪隻於飼養成長期間便較容易感 染肺部與肝臟的疾病,尤其容易感染黴漿菌肺炎,而飼料中大都為黃豆粕與 玉米粉,可能於高溫潮濕的環境中產生黃麴毒素,對肝臟造成病變,但對於 其他組織對照組則無任何病變產生。比較病變結果與組織中鉛含量,在急性 鉛暴露後,對所有組織器官可能會產生病變,但與組織中鉛含量並無絕對相 關,尤其是脾臟雖然鉛含量高於心臟、肺臟與大腦,但卻無任何病變產生。

Table 5-1 Comparison of lead concentration (µg/g) in tissues after with and without administration of lead nitrate.

Tissue Control 25 mg Pb/kg 50 mg Pb/kg Liver 0.053 a ± 0.019 3.519 b ± 0.363 3.978 b ± 0.783 Kidney 0.026 a ± 0.020 2.312 b ± 0.453 2.706 b ± 0.917 Spleen 0.032 a ± 0.012 0.277 b ± 0.030 0.350 b ± 0.056 Heart 0.027 a ± 0.004 0.130 b ± 0.036 0.143 b ± 0.034 Lung 0.018 a ± 0.002 0.094 b ± 0.005 0.101 b ± 0.015 Brain 0.008 a ± 0.003 0.061 b ± 0.013 0.091 b ± 0.017 Blood (µg/mL) 0.011 a ± 0.003 0.063 b ± 0.013 0.109 c ± 0.013

Table 5-2 Tissue lead concentration (µg/g) in the control group.

Tissue 43 44 46 Mean SE

Spleen 0.018 0.021 0.056 0.032 0.012 Kidney 0.003 0.009 0.065 0.026 0.020 Lung 0.015 0.018 0.021 0.018 0.002 Heart 0.024 0.022 0.036 0.027 0.004 Liver 0.090 0.036 0.032 0.053 0.019 Brain 0.004 0.006 0.015 0.008 0.003 Blood (µg/mL) 0.007 0.009 0.016 0.011 0.003

Table 5-3 Tissue lead concentration (µg/g) after 25.0 mg Pb/kg dosed.

Tissue 51 52 53 Mean SE

Spleen 0.255 0.336 0.240 0.277 0.030 Kidney 3.128 2.246 1.563 2.312 0.453 Lung 0.092 0.103 0.086 0.094 0.005 Heart 0.060 0.154 0.176 0.130 0.036 Liver 3.261 4.236 3.061 3.519 0.363 Brain 0.052 0.045 0.086 0.061 0.013 Blood (µg/mL) 0.054 0.047 0.089 0.063 0.013

Table 5-4 Tissue lead concentration (µg/g) after 50.0 mg Pb/kg dosed.

Tissue 47 48 49 Mean SE

Spleen 0.358 0.442 0.250 0.350 0.056 Kidney 4.163 2.942 1.014 2.706 0.917 Lung 0.100 0.127 0.076 0.101 0.015 Heart 0.080 0.197 0.153 0.143 0.034 Liver 3.934 5.356 2.644 3.978 0.783 Brain 0.062 0.121 0.089 0.091 0.017 Blood (µg/mL) 0.133 0.104 0.090 0.109 0.013

Table 5-5 Pathologic examination of tissue after oral 25.0 mg Pb/kg dosed

Tissue (µg/g) 51 52 53

Liver (肝臟) (3.519 ± 0.363)

Peri-portal fibrosing, bile duct hyperplasia, and portal triaditis, mild.

(門脈周區纖維化,膽管增生以及門脈三角區炎症反應,輕度)

Kidney(腎臟)

(2.312 ± 0.453)

Interstitial nephritis, lymphocytic, mild, focal, subacute.

(間質性腎炎,淋巴球性,

輕度,局部性,亞急性)

Interstitial nephritis, lymphocytic, minimal, focal, subacute, with mild renal tubular regeneration.

(間質性腎炎,淋巴球性,

(0.277 ± 0.030) No significant lesions. (無明顯病理病變) Heart ( 心 臟 )

No significant lesions.

(無明顯病理病變)

myocardium fibrosing, focal, mild, chronic (心肌纖維化,局部 性,輕度,慢性)

Lung(肺臟)

(0.094 ± 0.005)

Interstitial pneumonia, moderate, diffuse, chronic, with lymphoid nodular hyperplasia

(間質性肺炎,中度,瀰漫性,慢性,伴發類淋巴結 minimal, with acute neuronal degeneration.

(血管炎,淋巴球性,

局部性,輕微,伴發 急性神經元變性)

Liver:

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis, mild.

(門脈周區纖維化,膽管增生以及門脈三角 區炎症反應,輕度)

(HE Stain, 200x)

Kidney:

Interstitial nephritis (arrow), lymphocytic (broad arrow), mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,

亞急性)

(HE Stain, 200x)

Heart (Myocardium):

Myocarditis, lymphcytic (arrow), focal, mild.

(心肌炎,淋巴球性,局部性,輕度) (HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), moderate, diffuse, chronic, with lymphoid nodular hyperplasia (broad arrow).

(間質性肺炎,中度,瀰漫性,

慢性,伴發淋巴結節樣增生) (HE Stain, 200x)

Fig. 5-1 Pathologic examination data of tissue in pig No.51 after 25.0 mg Pb/kg dosed.

Kidney:

Interstitial nephritis, lymphocytic (arrow), minimal, focal, subacute, with mild renal tubular regeneration.

(間質性腎炎,淋巴球性,輕微,局部性,

亞急性,伴有輕度腎小管再生) (HE Stain, 200x)

Liver:

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis, mild.

(門脈周區纖維化,膽管增生以及門脈三角 區炎症反應,輕度)

(HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), moderate, diffuse, chronic, with lymphoid nodular hyperplasia (broad arrow).

(間質性肺炎,中度,瀰漫性,慢性,

伴發淋巴結節樣增生) (HE Stain, 200x)

Fig. 5-2 Pathologic examination data of tissue in pig No.52 after 25.0 mg Pb/kg dosed.

Kidney:

Mild interstitial fibrosing (arrow), focal, chronic.

(輕度間質性纖維化,局部性,慢性) (HE Stain, 200x)

Liver:

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis, mild.

(門脈周區纖維化,膽管增生以及門脈三角 區炎症反應,輕度)

(HE Stain, 200x)

Brain (Cerebrum):

Vasculitis (arrow), lymphocytes (broad arrow), focal, minimal, with acute neuronal degeneration (dot arrow).

(血管炎,淋巴球性,局部性,輕微,伴發 急性神經元變性)

(HE Stain, 200x)

Heart (Myocardium):

myocardium fibrosing (arrow), focal, mild, chronic.

(心肌纖維化,局部性,輕度,慢性) (HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), mild, multifocal, chronic.

(間質性肺炎,輕度,多發局部性,慢性) (HE Stain, 200x)

Fig. 5-3 Pathologic examination data of tissue in pig No.53 after 25.0 mg Pb/kg dosed.

Tissue (µg/g) 47 48 49

Liver(肝臟)

(3.978 ± 0.783)

Peri-portal fibrosing, bile duct hyperplasia, and portal triaditis, mild.

(門脈周區纖維化,膽管增 生,門脈三角區炎症反 應,輕度)

Peri-portal fibrosing, bile duct hyperplasia, and portal triaditis, mild.

(門脈周區纖維化,膽管增 生,門脈三角區炎症反 應,輕度)

Portal triaditis, mild, chronic, multifocal, with mild portal fibrosing, and megalocytosis.

No significant lesions.

(無明顯病理病變)

Interstitial nephritis, lymphocytic, mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,亞急性) Spleen(脾臟)

(0.350 ± 0.056) No significant lesions.(無明顯病理病變)

Heart ( 心 臟 ) (myocardium) (0.143 ± 0.034)

Cardiomyopathy,

coagulative degeneration, mild, multifocal, acute.

(心肌病,鬱血性變性,輕 度,多發局部性,急性)

Myocardial fibrosis, focal, mild, chronic, with

myocytolysis, fragmentation.

(心肌纖維化,局部性,輕 度,慢性,伴發心肌纖維 溶解,心肌纖維斷裂)

No significant lesions.

(無明顯病理病變)

Lung(肺臟)

(0.101 ± 0.015)

Interstitial pneumonia, mild, diffuse, chronic, with lymphoid nodular chronic, with lymphoid nodular hyperplasia, and emphysema.

(間質性肺炎,輕微,多發 局部性,慢性,伴發類淋 巴結節樣增生和肺氣腫)

Interstitial pneumonia, mild, multifocal, chronic, with lymphoid nodular hyperplasia. minimal, with laminal neuronal degeneration. multifocal, with mild neuronal degeneration (腦膜腦炎,淋巴球性,輕 度,多發局部性,伴發輕 度神經元變性)

Liver:

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis (dot arrow), mild.

(門脈周區纖維化,膽管增生以及門脈三角 區炎症反應,輕度)

(HE Stain, 200x)

Brain (Cerebrum):

Meningitis, lymphocytic (arrow), minimal.

(腦膜炎,淋巴球性,輕微) (HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), mild, diffuse, chronic, with lymphoid nodular hyperplasia (broad arrow).

(間質性肺炎,輕度,瀰漫性,慢性,併發 淋巴結節樣增生)

(HE Stain, 200x)

Heart (Myocardium):

Cardiomyopathy, coagulative

degeneration (arrow), mild, multifocal, acute.

(心肌病,凝固變性,輕度,多發局部性,

急性)

(HE Stain, 200x)

Kidney:

Interstitial nephritis (arrow),

lymphocytic, mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,

亞急性)

(HE Stain, 200x)

Liver:

Peri-portal fibrosing (arrow), bile duct hyperplasia, and portal triaditis, mild.

(門脈周區纖維化,膽管增生,

門脈三角區炎症反應,輕度) (HE Stain, 200x)

Brain (Cerebrum):

Neuronal degeneration (arrow), mild.

(神經元變性,輕度) (HE Stain, 200x)

Heart (Myocardium):

Myocardial fibrosis (arrow), focal, mild, chronic, with myocytolysis, fragmentation.

(心肌纖維化,局部性,輕度,慢性,伴發 心肌纖維溶解,心肌纖維斷裂)

(HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), minimal, multifocal, chronic, with lymphoid nodular hyperplasia (broad arrow), and emphysema (dot arrow).

(間質性肺炎,輕微,多發局部性,慢性,

伴發淋巴結節樣增生和肺氣腫) (HE Stain, 200x)

Fig. 5-5 Pathologic examination data of tissue in pig No.48 after 50.0 mg Pb/kg dosed.

Liver:

Portal triaditis (arrow), mild, chronic, multifocal, with mild portal fibrosing, and megalocytosis.

Interstitial nephritis, lymphocytic (arrow), mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,

亞急性)

(HE Stain, 200x)

Brain (Cerebrum):

Meningoencephalitis, lymphocytic, mild (arrow), multifocal, with mild neuronal degeneration

(腦膜腦炎,淋巴球性,輕度,多發局部性,

伴發輕度神經元變性) (HE Stain, 200x)

Lung:

Interstitial pneumonia (arrow), mild, multifocal, chronic, with lymphoid nodular hyperplasia (broad arrow).

(間質性肺炎,輕度,多發局部性,慢性,

伴發類淋巴結節樣增生) (HE Stain, 200x)

Fig. 5-6 Pathologic examination data of tissue in pig No.49 after 50.0 mg Pb/kg dosed.

Brain (Cerebrum): No lesions.

(無病理病變) (HE Stain, 200x)

Heart (Myocardium):

No lesions.

(無病理病變) (HE Stain, 200x)

Lung:

No lesions.

(無病理病變) (HE Stain, 200x)

Fig. 5-7 Pathologic examination data of tissue in the control group

Kidney:

No lesions.

(無病理病變) (HE Stain, 200x)

Liver:

No lesions.

(無病理病變) (HE Stain, 200x)

Spleen:

No lesions.

(無病理病變) (HE Stain, 200x)

Fig. 5-8 Pathologic examination data of tissue in the control group.

Liver:

No lesions.

(無病理病變) (HE Stain, 200x)

Liver: (25.0 mg Pb/kg)

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis, mild.

(門脈周區纖維化,膽管增生以及門脈三角區 炎症反應,輕度)

(HE Stain, 200x)

Liver: (50.0 mg Pb/kg

Peri-portal fibrosing (arrow), bile duct hyperplasia (broad arrow), and portal triaditis (dot arrow), mild.

(門脈周區纖維化,膽管增生以及門脈三角區 炎症反應,輕度)

(HE Stain, 200x)

Fig. 5-9 Comparison of pathologic examination data of liver among the three groups.

Heart: (control) No lesions.

(無病理病變) (HE Stain, 200x)

Heart: (25.0 mg Pb/kg)

Myocarditis, lymphcytic (arrow), focal, mild.

(心肌炎,淋巴球性,局部性,輕度) (HE Stain, 200x)

Heart: (50.0 mg Pb/kg)

Myocardial fibrosis (arrow), focal, mild, chronic, with myocytolysis, fragmentation.

(心肌纖維化,局部性,輕度,慢性,伴 發心肌纖維溶解,心肌纖維斷裂) (HE Stain, 200x)

Fig. 5-10 Comparison of pathologic examination data of heart among the three groups.

Lung: (control) No lesions.

(無病理病變) (HE Stain, 200x)

Lung: (25.0 mg Pb/kg)

Interstitial pneumonia (arrow), moderate, diffuse, chronic, with lymphoid nodular hyperplasia (broad arrow).

(間質性肺炎,中度,瀰漫性,慢性,伴發淋 巴結節樣增生)

(HE Stain, 200x)

Lung: (50.0 mg Pb/kg)

Interstitial pneumonia (arrow), minimal, multifocal, chronic, with lymphoid nodular hyperplasia (broad arrow), and emphysema.

(間質性肺炎,輕微,多發局部性,慢性,伴 發淋巴結節樣增生和肺氣腫)

(HE Stain, 200x)

Fig. 5-11 Comparison of pathologic examination data of lung among the three groups.

Kidney: (control) No lesions.

(無病理病變) (HE Stain, 200x)

Kidney: (25.0 mg Pb/kg) Interstitial nephritis (arrow), lymphocytic (broad arrow), mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,

亞急性)

(HE Stain, 200x)

Kidney: (50.0 mg Pb/kg) Interstitial nephritis (arrow), lymphocytic (broad arrow), mild, focal, subacute.

(間質性腎炎,淋巴球性,輕度,局部性,

亞急性)

(HE Stain, 200x)

Fig. 5-12 Comparison of pathologic examination data of kidney among the three groups.

Brain: (control) No lesions.

(無病理病變) (HE Stain, 200x)

Brain: (25.0 mg Pb/kg)

Vasculitis (arrow), lymphocytes (broad arrow), focal, minimal, with acute neuronal degeneration.

(血管炎,淋巴球性,局部性,輕微,伴發急 性神經元變性)

(HE Stain, 200x)

Brain: (50.0 mg Pb/kg)

Meningoencephalitis (arrow), lymphocytic, mild, multifocal, with mild neuronal degeneration

(腦膜腦炎,淋巴球性,輕度,多發局部性,

伴發輕度神經元變性) (HE Stain, 200x)

Fig. 5-13 Comparison of pathologic examination data of brain among the three groups.

六 結論

一、急性鉛暴露,對血液造成急性傷害,血紅素與紅血球的量降低,有貧血的現 象;同時白血球數量升高,體內產生炎症反應。

二、急性鉛暴露時,血液中的鉛含量無法表示組織鉛含量分佈情形與組織受損之 情形,但對組織器官造成嚴重傷害,尤其是腎臟。

三、藉由藥物動力學之血中鉛對時間作圖,可以作為急性鉛中毒或誤食含鉛化物 時,攝入量、攝入時間與身體器官傷害之參考,同時可以作為臨床預後之 診治。

未來研究方向

(一)鉛如何通過血腦障壁,危害神經系統?血中鉛與腦脊髓液中鉛之關係研究。

(二)鉛在骨髓中以何種形式結合蓄積?血液與骨髓中的鉛含量之相關變異情形 又是如何?不同濃度的鉛含量對骨髓幹細胞之影響研究。

(三)從事鉛作業的勞工健康檢查後,經判定為鉛中毒高危險群,依規定必須調

(三)從事鉛作業的勞工健康檢查後,經判定為鉛中毒高危險群,依規定必須調

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