臺灣博碩士論文加值系統

前列腺素為一多功能性調節物質，具有例如刺激平滑肌收縮、抑制胃酸分泌、促進血小板凝集、促進血管舒張等功能。前列腺素合成（cyclooxygenase）是花生四烯酸轉換成前列腺素E2（PGE2）的關鍵酵素。先前研究指出，炸油飲食會增加大鼠尿中Bicyclo PGE2及PGE2含量，並且會增加腎臟及儲精囊PGE2合成。另外經由腎臟免疫組織染色也可發現炸油飲食增加皮質部PG的合成、COX-2 mRNA及蛋白質表現量。顯示炸油飲食可能會影響大鼠腎臟中PGE2之合成。另一方面，炸油飲食亦會增加腎臟cytochrome P-450 4A1之表現量。此等因子可能與水及電解質平衡有關。因此，本研究目的在探討飲食炸油是否影響水分及鈉鉀平衡並進一步探討炸油飲食對大鼠腹腔巨噬細胞分泌PGE2之影響。
將麵片在205 ± 5℃之新鮮黃豆油中油炸，連續4天，每天油炸6小時，共24小時，供為實驗用油。將炸油分別以5%或20% (wt/wt) 配成低炸油 (LD) 及高炸油 (HD) 飼料，並以同量新鮮黃豆油配成低油 (LF) 及高油 (HF) 對照組飼料。20隻鼠齡為4週大的 Long-Evans雄鼠依體重隨機分成四組，分別餵食LD、HD、LF及HF四組飼料。餵養3週後，將大鼠移入代謝籠1週，記錄其每日之飲水量及飼料攝取量，每日收集並計量尿液及糞便排出量，凍存供分析尿液及糞便中之水分及鈉鉀含量。之後再將動物移回原不鏽鋼籠中，繼續以實驗飲食飼養三週後予以犧牲，取其腹腔細胞進行巨噬細胞體外培養。
飼養結果，以高炸油組 (HD) 的生長狀況最差，其體重增加量僅及HF組之75% (P＜0.05) ，低炸油組與兩組對照組之體重增加並無顯著差異 (P＞0.05)。炸油組尿中Bicyclo PGE2含量顯著高於新鮮油組（P＜0.05）。在鈉鉀等電解質平衡方面，HD組因攝食量較低，故鈉鉀之每日攝入量顯著較低 (P＜0.05)。尤有甚者，HD組自糞便排出之鈉、鉀含量分別為HF之23倍與12倍 (P＜0.05)。因此，HD組之外表鈉、鉀吸收量分別約只有HF組的65%及85% (P＜0.05)。因是之故，HD組之尿中鈉、鉀排出量也較HF組低。將鈉鉀攝取量扣除糞便及尿中排出量，計算外表鈉鉀之平衡，炸油組之鈉鉀平衡值高於新鮮油組 (P＜0.05)。餵食炸油鼠保留於體內之鈉、鉀量佔吸收量及攝取量之比率亦顯著較高 (P＜0.05)。本實驗結果顯示，炸油飼料使鼠體內保留較多的鈉，並傾向飲用較多水並排出較多尿。而高炸油飲食嚴重干擾鈉、鉀之吸收，但鼠體亦以降低尿排出量以維持鈉鉀平衡。但由鈉、鉀淨平衡值仍然較高的結果看來，炸油似有促鈉鉀保留之效應。
在腹腔巨噬細胞方面，空白處理組之PGE2的生成量以HD組為最高，但和HF組比較則無顯著差異（P＞0.05）；以LPS處理組為正向控制組（positive control），結果顯示LPS會增加大鼠腹腔巨噬細胞PGE2分泌及COX-2蛋白質表現；以大鼠血清處理腹腔巨噬細胞組，則以高炸油鼠血清培養HD組大鼠腹腔巨噬細胞顯著的增加PGE2的分泌量(P＜0.05)，但不會增加COX-2蛋白質表現量，可見其不是因為誘發COX-2表現來增加PGE2的合成量。

Prostaglandins are a lipid-derived mediator, that may exert a great variety of diverse functions, such as: stimulating smooth muscle contraction, inhibiting gastric acid secretion, enhancing platelet aggregation and vasodilation, etc. Cyclooxygenase (COX) is the key enzyme which catalyzes the first two steps in the biosynthesis of prostaglandins E2 (PGE2) from arachidonic acid. Previously, it was shown that urinary PGE2 and bicyclo PGE2, the metabolite of PGE2, increased significantly in rats fed oxidized frying oil (OFO). OFO also enhanced the PGE2 levels in the kidney and seminal vesicle. Besides, it was also shown that OFO enhanced COX-2 protein expression in renal cortex rats indicated by immunohistochemistry. On the other hand, OFO also enhanced cytochrome P-450 4A1 expression in rats’ kidney. As these factors are known to be involved in the regulation of water and electrolyte balance, the main aim of this study was to investigate whether water, sodium and potassium balance can be influenced by dietary OFO. Moreover, we were also interested in confirming the effect of dietary OFO on the PGE2 production of peritoneal macrophages in rats.
OFO sample was obtained by frying dought sheet in soybean oil in a cast iron work under 205 ± 5℃ for 24 hours. Four groups of male Long-Evans weanling rats were fed respectively the two test diets, namely, LD ( containing 5% OFO ) and HD ( containing 20% OFO ), and the two control diet, namely, LF ( containing 5% fresh soybean oil ) and HF ( containing 20% fresh soybean oil ) for 3 weeks. Rats were then moved into metabolic cages for one week to record their daily water and food intake and to collect their daily urine and fece excretion. Urine and fecal samples were analyzed for water, sodium and potassium content to evaluate the absorption and balance. Then rats were moved back to their original cages for three more weeks. At the end of the feeding period, the rats were sacrificed and peritoneal macrophages collected and cultured.
HD group of rats showed significantly lower body weight gain than the remaining 3 groups of rats. The body weight gain of the HD group was only 75 % that of the HF group (P＜0.05). There were no significant difference in the body weight gain among LD, LF and HF groups (P＞0.05). Concerning sodium and potassium balance, HD group had the lowest daily sodium and potassium intake (P＜0.05) because of the lowest daily food intake of this group. Furthermore, the fecal sodium and potassium excretion of the HD group were 23 and 12 times that of the HF group, respectively. Thus, the sodium and potassium absorbed by the HD group were approximate 65% and 85% that of the HF group, respectively. The excretions of urinary sodium and potassium of the HD group were also lower than the HF group. The positive sodium and potassium balance of LD and HD groups were significantly higher than LF and HF groups (P＜0.05). The result indicated that dietary OFO lead to more sodium retained in the body, made rats fed OFO tended to drink more water and excreted higher amount of urine. A high OFO diet marked by reduced the sodium and potassium absorptions of rats. In response, urinary excretion of these electrolytes also decreased significantly to maintain a homeostasis. However, the sodium and potassium balance were finally higher in rats fed OFO diets, implying dietary OFO tended to retained more sodium in the body.
The peritoneal macrophage of the HD group cultured in medium containing 10% serum of the HD group rats produced significantly higher PGE2 (P＜0.05), but did not express more COX-2 protein. These data confirmed previous observations that dietary OFO enhanced PGE2 production of macrophages. Furthermore, this enhancement was not due to a higher expression of the COX-2 protein.

中文摘要Ⅰ
英文摘要Ⅲ
縮寫對照表Ⅴ
第一章 緒言1
第一節前言1
第二節 文獻回顧2
一、前列腺素 E2 ( Prostaglandin E2, PGE2 )2
(一)Eicosanoid2
(二)Prostanoids4
(三)PGHS合成  / Cyclooxygenase5
(四)環氧化 ( cyclooxygenase , COX ) 同功的發現7
二、環氧化、前列腺素E2與腎臟功能8
(一)COX-1及COX-2在腎臟的表現位置8
(二)前列腺素E 受器 ( PGE receptors ) 與腎臟功能11
(三)PGHS knockout mice13
(四)飲食中鹽含量對腎臟COX表現之影響14
(五)PGE2調控腎臟水分及鈉離子的再吸收作用15
(六)Renin釋放的調節15
三、Cytochrome P-450 代謝產物20-hydroxyeicosatetraenoic
acid (HETE) 與Kidney之間的關係16
四、受熱油脂對動物之影響16
(一)油脂在油炸時之化學變化16
(二)炸油對動物體之影響17
第三節 實驗動機與目的18
第二章 飲食炸油對鈉鉀平衡之影響20
第一節 前言20
第二節 實驗大綱20
第三節 材料與方法21
一、炸油之製備21
二、試驗飼料的製備21
三、動物飼養、體重變化及攝食情形22
四、外表水分平衡與鈉鉀平衡之觀察22
五、飼料中鈉鉀含量之分析23
六、尿液分析24
(一)尿液中Bicyclo PGE2含量之測定24
(二)尿液中前列腺素E2 (Prostaglandin E2, PGE2) 的測定25
(三)尿液中鈉鉀濃度的測定27
(四)尿液中肌酸酐 (creatinine) 含量之測定28
七、糞便分析29
(一)糞便中水分含量之測定29
(二)糞便中鈉鉀含量之分析29
八、計算水、鈉、鉀之外表吸收與平衡29
(一)外表吸收量29
(二)外表平衡量(保留量)29
(三)保留量佔吸收量之百分率（%）29
(四)外表吸收率29
(五)外表保留率30
九、統計分析29
第四節 結果30
一、動物生長及攝食狀況30
(一)動物生長狀況30
(二)動物攝食情形30
二、各組飼料中鈉鉀含量30
三、各組大鼠尿中Bicyclo PGE2及PGE2排出量31
四、飲食炸油對大鼠外表鈉吸收、平衡與保留之影響31
(一)鈉攝取量31
(二)糞便鈉排出量32
(三)外表鈉吸收及吸收率32
(四)尿液鈉排出量32
(五)外表鈉平衡33
(六)攝取與吸收的鈉在體內保留情形33
五、飲食炸油對大鼠外表鉀吸收、平衡與保留之影響33
(一)鉀攝取量33
(二)糞便鉀排出量34
(三)外表鉀吸收及吸收率34
(四)尿液鉀排出量34
(五)外表鉀平衡35
(六)攝取與吸收的鉀在體內保留情形35
六、飲食炸油對大鼠外表水份吸收、平衡與保留之影響35
(一)水分攝取量35
(二)糞便水分排出量36
(三)尿液水分排出量36
(四)外表水分平衡36
(五)外表水分之吸收率與保留率36
第五節 討論48
一、動物生長及攝食狀況48
二、飲食炸油增加尿中PGE2及PGE2代謝產物Bicyclo PGE2的含量48
三、飲食炸油對大鼠外表鈉鉀與水分吸收與保留之影響49
四、高炸油飲食降低尿鈉排出量的可能原因50
第六節 結論51
第三章 飲食炸油對大鼠腹腔巨噬細胞之影響52
第一節 前言52
第二節 實驗大綱53
第三節 材料與方法54
一、動物飼養、體重變化及攝食情形54
二、動物犧牲與血液樣品樣品收集54
(一)動物犧牲54
(二)血液樣本的收集54
三、腹腔巨噬細胞培養用之血清取得54
四、腹腔巨噬細胞之取得與培養55
(一)實驗流程55
(二)腹腔巨噬細胞之取得57
(三)腹腔巨噬細胞之培養58
五、腹腔巨噬細胞培養液及蛋白質之分析59
(一)細胞上清培養液PGE2之分析59
(二)腹腔巨噬細胞COX-2蛋白質表現量之測定59
六、血漿中各種脂質成份分析63
(一)血漿總脂肪量(Total Lipids)之測定63
(二)血漿三酸甘油酯（Triacylglycerol, TG）含量之測定63
(三)血漿膽固醇(Cholesterol)含量之測定64
(四)血漿磷脂質 (Phospholipid)含量之測定64
(五)血漿游離脂肪酸總量(Non-Esterified Fatty Acid, NEFA)含量之
測定65
七、統計分析65
第四節 結果66
一、動物生長及攝食狀況66
二、相對組織重量66
三、大鼠腹腔巨噬細胞數目66
四、各處理組之腹腔巨噬細胞分泌PGE2之情形66
五、各處理組之腹腔巨噬細胞Cyclooxygenase-2蛋白質含量67
六、血漿中各種脂質分析結果67
第五節 討論74
一、相對組織重量74
二、炸油飲食對大鼠腹腔巨噬細胞之影響74
第四章 總結76
第五章 參考文獻77

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