十三味安胎飲(Thirteen Herbs An-Tai In, THATI)湯劑(當歸、白芍、川芎、枳殼、厚朴、黃耆、川貝母、羌活、荊芥、菟絲子、艾葉、甘草、乾薑) 是中醫歷代醫家常用安胎方劑，一般坊間即可自行購得。鑒於十三味安胎飲普受懷孕婦女服用，目前當務之急為對其可能具有的潛在遺傳毒性進行科學評估，本論文利用偵測染色體傷害之微核技術來探討十三味安胎飲對於孕鼠與其胎鼠是否會誘發遺傳物質損傷，以及十三味安胎飲對於化學毒物是否有化學保護效果。以母鼠檢查出陰栓日為懷孕第一日，將懷孕ICR母鼠分成四大組，1.陰性對照組：胃管餵食去離子水；2.陽性對照組：胃管餵食去離子水後，於懷孕第十七日腹腔注射(ip)化學致癌劑N-ethyl-N-nitrosourea (ENU) 90mg/Kg；3.中藥餵食組：於懷孕第七日至第十七日或懷孕第十二日至第十七日，胃管餵食十三味安胎飲浸膏，檢測中藥浸膏是否會誘發遺傳毒性﹔4.化學預防組：餵食十三味安胎飲浸膏後，ip投與ENU，藉以檢測十三味安胎飲對致癌劑誘發之遺傳毒性是否具有保護效果。第十九日採孕鼠與胎鼠周邊血作抹片，以計數周邊血網狀紅血球(reticulocytes, RET)的微核發生率。結果顯示，在孕鼠餵藥過程中，各組之體重增加率在統計上並無明顯差異，各組之周邊血網狀紅血球與正染紅血球(normochromatic erythrocytes, NCE)的比值(RET/NCE)也無差異性，而胎鼠RET/NCE值明顯高於孕鼠。ENU投藥後24小時(懷孕第十八天)採血，孕鼠微核發生率並無明顯增加，ENU之致突變效應在投藥後48小時(即第十九日)才顯現出來，於1000個RET中孕鼠微核平均數為21.8個，明顯高於陰性對照組的1.3個。ENU會通過胎盤使胎鼠微核率增加，但胎鼠之微核發生率明顯低於孕鼠。懷孕第十二日至第十七日餵食十三味安胎飲(17.55g生藥/kg，三倍臨床劑量)組，孕鼠與其胎鼠微核發生率與陰性對照組比較並無顯著增加，懷孕第七天至第十七天餵食組也得到類似的結果。結果發現連續餵食孕鼠十三味安胎飲達三倍臨床劑量，對孕鼠沒有明顯的染色體遺傳毒性，也不會透過胎盤引起胎鼠染色體損傷，本實驗結果可作為孕婦中藥服用安全性考量的參考。另方面化學預防組與陽性對照組相比較並無顯著差異，顯示在此實驗條件中，十三味安胎飲亦無明顯的化學預防效果。; Chinese herbal medicine “Thirteen Herbs An-Tai In“ (THATI) has been traditionally used as the anti-abortion medicine. Due to its extensive use, it is of great concern referring to its genotoxic potential to pregnant women and their offspring. In this study, we determined the potential genotoxic and chemopreventive effects of THATI in pregnant ICR mice and their fetuses using Micronuclei assay. Four experimental groups had been conducted. For the negative control group, the pregnant mice were given with distilled water only from gestation day (GD) 12 through 17. For the positive control group, N-ethyl-N-nitrosourea (ENU) was given by intraperitoneal injection (ip) at a dose of 90mg/kg on GD 17 after water treatment from GD 12 to 17. For THATI genotoxicity group, aqueous extracts of THATI were given by gavage from GD 12 to 17. For THATI chemoprevention group, ENU was administered on GD 17 after THATI treatment from GD 12 to 17. Blood samples were collected on GD 19 to examine the frequencies of micronuclei in maternal and fetal reticulocytes (RET), a marker for chromosome damage. There is no statistically significant difference among the four experimental groups in maternal body weight gain and RET/normochromatic erythrocytes (NEC) ratio. However, RET/NEC ratios in fetuses were markedly higher than those in pregnant dams. Treatment of THATI at the dose of 17.55g/kg and 5.85g/kg did not induce a statistically significantly increase in frequencies of micronuclei in maternal and fetal reticulocytes. Moreover, pretreatment with THATI resulted in no observable decrease in the frequencies of ENU-induced micronucleated reticulocytes. These data suggest that THATI did not have a genotoxic or chemopreventive effects in mice.
