目的 通過豚鼠離體回腸模型及小鼠類致敏實(shí)驗(yàn)評(píng)價(jià)注射用益氣復(fù)脈（凍干，YQFM）的安全性。方法 建立豚鼠離體回腸模型，依次考察0.2、0.4、0.6、0.8、1.2、1.4、1.6 mg/mL質(zhì)量濃度的YQFM對(duì)靜息離體腸、乙酰膽堿（Ach）及組胺（His）誘導(dǎo)的離體腸收縮的抑制率；雄性ICR小鼠隨機(jī)分為陰性對(duì)照組，陽性對(duì)照組（C48/80，25 mg/kg），YQFM低、高劑量（780、3 135 mg/kg，分別為臨床等效劑量的0.85和3.43倍）組，分為尾iv含0.4%伊文思藍(lán)（EB）的藥液及不含0.4% EB的藥液兩部分進(jìn)行體內(nèi)類致敏反應(yīng)實(shí)驗(yàn)，依次比較各組小鼠耳廓藍(lán)染情況；ELISA法測(cè)定血清中His和5-羥色胺（5-HT）的含量；并對(duì)耳、肺組織進(jìn)行HE染色及病理檢查。結(jié)果 體外實(shí)驗(yàn)顯示，YQFM既能夠抑制離體腸的自主收縮，又能抑制Ach和His導(dǎo)致的離體腸痙攣；體內(nèi)實(shí)驗(yàn)表明，YQFM低劑量組耳廓藍(lán)染率，His、5-HT含量均在正常范圍，組織病理檢查未見明顯異常；3.43倍臨床等效劑量時(shí)耳廓藍(lán)染率，His、5-HT含量略高，病理結(jié)果見輕微炎癥反應(yīng)。結(jié)論 YQFM的安全性基本良好，臨床使用時(shí)需對(duì)使用劑量稍加注意，以防輕微不良反應(yīng)發(fā)生。

Objective To evaluate the safety of Yiqi Fumai Lyophilized Injection (YQFM) by using guinea pig isolated ileum model and pseudo-allergic reaction. Methods Isolated guinea pig ileum, resting ileum, acetylcholine (Ach) and histamine (His) load ileum were used as research models. And these models were used to detect different concentrations of YQFM (0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, and 1.6 mg/mL). Male ICR mice were randomly divided into negative control group, positive control (C48/80, 25 mg/kg) group, and YQFM low and high dose (780 and 3135 mg/kg, 0.85 and 3.43 times of clinical equivalent dose respectively). Mice were divided into two parts like iv injections containing 0.4% Evans blue (EB) and injections without 0.4% EB for pseudo-allergic reaction test. This research evaluated auricular blue dye of mice in each group, the level of His and 5-hydroxytryptamine (5-HT) in serum and used HE staining to do ear and lung tissue pathological examination. Results In vitro experiments showed that YQFM could inhibit not only the voluntary contraction of ileum, but also Ach and His induced guinea pig ileum spasm. In vivo experiments showed the pinna blue dye rate, His, serotonin levels the low dose of YQFM group were in the normal range, and histopathological examination showed no significant abnormalities. Meanwhile, the high dose of YQFM could cause less pseudo-allergic reactions and His, serotonin levels were slightly higher than normal. Pathological findings showed a slight inflammatory reaction. Conclusion It was safety in the normal dose rang of YQFM. However, it was also need pay attention to the safety of using use high dose of it in clinical.

天津市中藥注射劑關(guān)鍵技術(shù)校企協(xié)同創(chuàng)新實(shí)驗(yàn)室建設(shè)（17PTSYJC00090）