銀杏葉萃取液對十二指腸潰瘍老鼠黏膜修復之影響

Effects of Ginkgo biloba on duodenal ulcer healing in rats

洪慧珍(Huei-Chen Hung)

指導教授 ： 趙振瑞

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2002年)

摘要

本研究目的為探討銀杏萃取液對十二指腸潰瘍老鼠黏膜修復之 影響。將大白鼠隨機分成四組：控制組（無潰瘍無銀杏治療）、無潰瘍銀 杏治療組、潰瘍無銀杏治療組，及潰瘍銀杏治療組。無潰瘍老鼠做剖腹假 手，潰瘍老鼠則以50%醋酸誘發十二指腸潰瘍。術後銀杏治療組老鼠從 尾靜脈注射0.5毫克銀杏萃取液/公斤體重/天，無銀杏治療組老鼠則以尾 靜脈注射等量不含銀杏之溶劑(vehicle)。7天和14天後，分析十二指腸黏 膜中細胞防禦因子，包括前列腺E2(prostaglandin E2; PGE2)和銅,鋅-超氧化 岐化酶(Cu,Zn-superoxidedismutase; Cu,Zn-SOD)活性，同時亦測量紅血球 中Cu,Zn-SOD酵素活性和血漿中脂質過氧化物濃度，以評估血漿中氧化 傷害的情形。病理切片結果顯示注射7天銀杏後,潰瘍銀杏治療組十二指 腸黏膜修復和發炎情形,較潰瘍無銀杏治療組改善。14天後，潰瘍無銀杏 治療組的體重較控制組為低。然而，潰瘍銀杏治療組老鼠的體重明顯較 潰瘍無銀杏治療組為高，但與控制組無差異。14天後，潰瘍銀杏治療組 黏膜中PGE2濃度分別較潰瘍無銀杏治療組和控制組明顯增加56% 和 52%(p < 0.05)。此外，14天後，黏膜和紅血球超氧化岐化酶活性於潰瘍 無銀杏治療組顯著較控制組下降;潰瘍銀杏治療組其紅血球酵素活性則 顯著高於潰瘍無銀杏治療組，而與控制組無差異。此外，7天和14天後， 潰瘍無銀杏治療組之血漿脂質過氧化物濃度皆比控制組高，潰瘍銀杏治 療組其脂質過氧化物濃度則較潰瘍無銀杏治療組顯著下降;但無潰瘍銀 杏治療組其脂質過氧化物濃度則皆高於控制組。由以上結果可發現：潰 瘍的確會導致老鼠體重下降、黏膜修復速度減慢、黏膜中PGE2濃度下 降、黏膜和紅血球中超氧化岐化酶性降低，及血漿脂質過氧化情形加 劇。而注射14天銀杏萃取液後，可明顯改善十二指腸潰瘍老鼠體重下 降、增加十二指腸黏膜中PGE2濃度和紅血球中超氧化岐化酶活性，並 減少血漿中脂質過氧化濃度。

關鍵字

銀杏葉萃取液 ； 十二指腸潰瘍 ； 前列腺素E2 ； 超氧化岐化酶脂質過氧化 ； 老鼠

並列摘要

This study was to investigate the effects of Ginkgo biloba extract on mucosal healing in duodenal ulcer rats. Sprague-Dawley rats were randomly divided into four groups: control (no ulcer without Ginkgo treatment), no ulcer with Ginkgo treatment, ulcer without Ginkgo treatment, and ulcer with Ginkgo treatment. Rats without ulcer were done by sham operation, and rats with duodenal ulcer were induced by 50% acetic acid. Rats with Ginkgo treatment were injected with Ginkgo biloba extract solution at a dose of 0.5 mg/kg body weight/day from the tail vein, and rats without Ginkgo treatment were i.v. injected with the same amount of vehicle solution without Ginkgo. After 7 and 14 days, cytoprotective factors, including prostaglandin E2 (PGE2) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity, in duodenal mucosa were analyzed. Additionally, erythrocyte Cu,Zn-SOD activity and plasma lipid peroxides were measured to evaluate the oxidative damage in the plasma. The pathological results showed that mucosal healing and inflammation improved in ulcer with Ginkgo group compared with ulcer without Ginkgo group after 7 days. After 14 days, body weight of ulcer without Ginkgo group was lower compared with that of the control group. However, body weight of ulcer with Ginkgo group significantly increased compared with ulcer without Ginkgo group, but did not differ from that of the control group. Mucosal PGE2 concentration significantly increased by 56% and 52% (p < 0.05) in ulcer with Ginkgo group compared with ulcer without Ginkgo and the control groups, respectively, after 14 days. Additionally, after 14 days, mucosal and erythrocyte SOD activity significantly decreased in ulcer without Ginkgo group compared with the control group. However, mucosal SOD activity significantly decreased in without ulcer with Ginkgo group compared with the control group. Erythrocyte SOD activity significantly elevated in ulcer with Ginkgo group compared with ulcer without Ginkgo group, but did not differ from the control group. After 7 and 14 days, plasma lipid peroxides significantly increased in ulcer without Ginkgo group compared with the control group. With ulcer with Ginkgo group had lower lipid peroxides than ulcer without Ginkgo group. However, lipid peroxides significantly increased in without ulcer with Ginkgo group compared with the control group. The results suggested that ulcer did cause decreases in body weight, the healing rate of the mucosa, mucosal PGE2 concentration, mucosal and erythrocyte SOD activity, and an increase in plasma lipid peroxides. Injected with Ginkgo biloba extract for 14 days, body weight, mucosal PGE2 concentration, and erythrocyte SOD activity significantly increased, and plasma lipid peroxides significantly decreased in duodenal ulcer rats. Key words: Ginkgo biloba extract, duodenal ulcer, prostaglandin E2, superoxide dismutase, lipid peroxidation, rats

參考文獻

Bowen J, Kuo Y-J, Pawlik D, Williams L, Shanabour L and Jacobson D (1975) Electrophysiological effects of burimamide and 16,16-dinethyl prostaglandin E2 on the canine gastric mucosa. Gastroenterology 68:1480-1484.

Chow SL and Hollander D (1979) Linoleic acid absorption in the unanesthetized rat: mechanism of transport and influence of luminal factors on absorption rate. Lipids 14:378-385.

Curtis-Prior P, Vere D and Fray P (1999) Therapeutic value of Ginkgo biloba in reducing symptoms of decline in mental function. J Pharm Pharmacol 51:535-541.

Elserier, Paris. De Feudis F V (1998) Ginkgo biloba extract(EGb761): from chemistry to clinic. Publr Ullestein Med and Weisbaden, Germany de la Hunt MN , Hillier K Jewell R (1988) Modification of upper gastrointestinal prostaglandins synthesis by dietary fatty acids. Prostaglandins 35:597-608.

Dinan M, Jaiswal K, Narimantas C, Dickacaite E and Juan S (1999) Quiercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Radic Biol Med 26:107-116.