| 摘要: | 研究背景與目的: 近年來，行政院衛生署中醫藥委員會為了提升國人在使用中藥上的用藥安全，推行了數年的相關計畫，包括中藥基原的鑑定、誤用混用、包裝、毒性試驗，以至於中西藥之增效減毒、用藥安全宣導以及中藥藥典的編撰。雷公藤是衛矛科雷公藤屬多年生木本植物。在本草綱目拾遺中，雷公藤被用做為殺蟲劑，但近年來有越來越多研究探討雷公藤在腎臟疾病及免疫性疾病上的治療效果，在免疫抑制方面，雷公藤是最強的中藥之一。但因為雷公藤的有效成分極有可能是有毒成分，且雷公藤的安全範圍狹窄，所以如何謹慎小心的使用雷公藤，以達到最大的藥效最小的毒性，是值得更進一步被探討的。本研究目的在於證明雷公藤不同部位的萃取物，像是地上部分的莖和地下部分的根及根皮，在使用不同劑量下對於腎臟及肝臟所造成的毒性。研究材料與方法: 雷公藤（Tripterygium
wilfordii Hook.）是衛矛科雷公藤屬的多年生木本植物，多生長在背陰、多濕稍肥的山坡山谷、溪邊濃木林及次生雜木林中。分布於浙江、江西、安徽、湖南、廣東、福建、雲南以及台灣等地。在台灣則多分布於基隆金瓜石、台北縣石碇或台北市內湖一帶的海岸或山坡。可於基隆金瓜石、台北縣石碇的山坡區進行野外採集。本研究中所使用的雷公藤為98 年初春及夏末採集於南投縣仁愛鄉以及台北縣石碇山坡，經由植物組織切片鑑定基原正確後使用。使用雷公藤不同部位進行萃取，然後進行急性毒性試驗與連續28 天給藥之劑量與毒性之探討。結果與討論: 本研究首先進行雷公藤之急性毒性試驗，結果發現，不同季節採收的雷公藤，其毒性含量也有所差異。根據實驗結果發現，初春採集的雷公藤莖跟葉的接近無毒，LD50 大於10g/kg；而在夏末採集的雷公藤，則依部位的不同毒性也有不同，地上部(莖)之LD50 為3.53 g/kg，葉之LD50 為5.06 g/kg；地下部去皮(根)之
LD50 為3.95 g/kg，地下部之根皮LD50 為1.67 g/kg；而從大陸山東省濟南市所購得之飲片，其LD50 亦大於10 g/kg。而各部位之萃取物以sublethaldose 投予大鼠後，進行肝腎毒性的評估，結果在肝腎均未發現明顯之病變情形。而連續給藥28 天後，大鼠進行解剖，觀察劑量與動物毒性的關聯性，檢驗包括：血液學檢查、血液生化檢查、尿液檢查以及病理檢查等，以了解雷公藤各部位之萃取物其劑量與毒性之關係及對於肝腎等臟器的影響。尿液的檢查結果沒有明顯的變化。而在血清生化值的結果中可以發現，給予去皮之根或根皮的萃取物組別中，不論是在高、中或低劑量組，和對照組相比，都可以發現在白血球的量明顯的增高；而給予根皮高劑量組的大鼠血液中ALT 和對照組相比，也有明顯的增加。而在凝血測試中可以發現，給予根皮萃取物的組別，其APTT 的時間明顯的較其他各組來的高。在病理
組織切片中發現，給予高劑量的根皮萃取物組，在腎臟切片中有發現發炎的現象；在肝臟病理切片部分，在各組均沒有明顯的病理變化。
Introduction: In order to conserve the medication security in Chinese medicine,
the Committe on Chinese Medicine and Pharmacy, Department of Health,
Executive Yuan had carried out several plans about the medication security in
Chinese medicine for several years. Identify with Chinese medicine, using
mistake, package, toxicity, increase or decrease the effect or toxicity when
combined use of the Chinese medicine and medicine, trumpet the medicine
security and compose the Chinese medicine pharmacopoeia were included in
those plans. Tripterygium wilfordii, a plant of the genus Tripterygium of the
family Celastraceae, is a root of a perennial liana. Owing to the narrow
therapeutic window, the active ingredient maybe the poison composition
ingredient. How to increase the safety in use of Tripterygium wilfordii is
important. The aim of this study is to demonstrate the relationship between
different parts of Tripterygium wilfordii, such as stem, root and root cortex, and
different dose with the toxicity in the liver and kidney. Materials and methods:
In this study, the crude material of Tripterygium wilfordii was collected in early
spring and late summer from Ren-ai Township, Nantou County and Shih-ding
Township, Taipei County. After identify the origin of Tripterygium wilfordii,
methanol was used to extract the crude material of Tripterygium wilfordii. The
rats treated with different dosages of the extraction of every part of the
Tripterygium wilfordii continuous for 28 days, sacrificed in the end of the
experience, to demonstrate the relationship between dosage and toxicity in rats’
liver and kidney, including blood test, biochemical test, urine test and pathology
test. Results and discussion: Results from acute toxicity test revealed that the
toxicity of Tripterygium wilfordii harvested from different season is not the
same. Crude material of Tripterygium wilfordii collected in the early spring is
nearly non-toxic; however, those collected in the late summer showed different
toxicity. LD50s of stem and leaf are 3.53g/kg and 5.06g/kg, respectively. LD50s
of root without cortex and root cortex are 3.95g/kg and 1.67g/kg, respectively.
LD50 of the commercial available material of the Tripterygium wilfordii bought
from China was over than 10g/kg. Results from rats treated with sublethal dose
of the Tripterygium wilfordii revealed no significant pathological changes in the
liver and kidney. Results from the routine urine tests were not significantly
different. Results from the blood routine could find the WBC count were higher
in treated with root and root cortex group than blank; the result of ALT in treated
with high cortex dose group was significantly increased compared with blank.
Results from blood coagulation test, times of APTT were longer in treated with
root cortex group than other group. In pathological histopathology, there were
nephritis, and postmortem could find diffuse in treated with high root cortex
dose group in kidney, but there was no significant change in liver in every
group. |
