[關(guān)鍵詞]
[摘要]
目的 利用斑馬魚模型評(píng)價(jià)血必凈注射液與3種抗生素并用對(duì)肝臟損傷的影響。方法 以肝臟熒光標(biāo)記的斑馬魚為動(dòng)物模型,設(shè)置對(duì)照組、抗生素單用(阿莫西林克拉維酸鉀分散片1 000 μg/mL、左氧氟沙星片800 μg/mL、阿莫西林膠囊400 μg/mL)組、血必凈注射液(2.5、5.0、10.0 μg/mL)+抗生素組,連續(xù)給藥72 h,每24 h更換暴露液,給藥結(jié)束后,顯微鏡下拍照,統(tǒng)計(jì)肝面積、肝臟熒光強(qiáng)度。收集樣品,石蠟包埋,切片,HE染色,進(jìn)行組織病理學(xué)檢查。結(jié)果 在阿莫西林克拉維酸鉀分散片和血必凈注射液的安全濃度范圍內(nèi)聯(lián)合用藥未發(fā)現(xiàn)斑馬魚死亡,未發(fā)現(xiàn)毒性加劇;在左氧氟沙星片和血必凈注射液的安全濃度范圍內(nèi)聯(lián)合用藥未發(fā)現(xiàn)斑馬魚死亡,未發(fā)現(xiàn)毒性加?。辉诎⒛髁帜z囊的安全濃度范圍內(nèi),聯(lián)合應(yīng)用10 μL/mL血必凈注射液可導(dǎo)致斑馬魚全部死亡;聯(lián)合應(yīng)用5 μL/mL血必凈注射液可導(dǎo)致部分斑馬魚死亡,剩余斑馬魚肝毒性加劇,與阿莫西林膠囊單用組比較,肝面積及肝臟熒光強(qiáng)度均顯著下降(P<0.05)。結(jié)論 血必凈注射液與阿莫西林克拉維酸鉀分散片、左氧氟沙星片并用不會(huì)對(duì)斑馬魚的肝臟造成損傷。阿莫西林膠囊與血必凈注射液并用時(shí)增加斑馬魚的肝損傷風(fēng)險(xiǎn),應(yīng)控制阿莫西林膠囊的處方濃度,并重點(diǎn)觀察患者肝功能變化。
[Key word]
[Abstract]
Objective To evaluate the effects of Xuebijing Injection and three kinds of antibiotics on liver protection and liver injury by zebrafish model. Methods Zebrafish with liver fluorescent labeling were used as animal models. The control group, single antibiotic group (amoxicillin clavulanate potassium dispersible tablet 1 000 μg/mL, levofloxacin tablet 800 μg/mL, amoxicillin capsule 400 μg/mL), Xuebijing Injection (2.5, 5.0, 10.0 μg/mL) + antibiotic group were set for continuous administration for 72 h. Change the exposure solution every 24 hours, After administration, the liver area, and liver fluorescence intensity were counted. Samples collection, paraffin embedding, paraffin section, HE staining, and histopathological examination were performed. Results The experimental results showed that there were no death and no aggravation of toxicity within the safe dose range of amoxicillin-clavulanate potassium, combing with Xuebijing (2.5, 5, 10 μL/mL). With the increasing of Xuebijing concentration, the liver area and fluorescence intensity increased gradually. Within the safe dose range of levofloxacin, no increase in toxicity was found combing with Xuebijing (2.5, 5, 10 μL/mL). Within the safe concentration range of amoxicillin, combined application of 10 μL/mL Xuebijing Injection could cause death of all zebrafish. The combined application of 5 μL/mL Xuebijing Injection could cause the death of some zebrafish, and the liver toxicity of the remaining zebrafish was aggravated. Compared with the group of amoxicillin capsule alone, the liver area and liver fluorescence intensity were significantly decreased (P < 0.05). Conclusion The combined use of Xuebijing Injection and amoxicillin-clavulanate potassium will not cause damage to the liver of zebrafish. The combined use of amoxicillin and Xuebijing Injection will increase the risk of liver injury in zebrafish, and high doses may lead to death. When using Xuebijing Injection clinically, the prescribed dose of amoxicillin should be controlled and the changes in liver function should be observed. The combined use of Xuebijing Injection and levofloxacin has not found any damage to the liver of zebrafish.
[中圖分類號(hào)]
[基金項(xiàng)目]
國(guó)家“萬人計(jì)劃”(2016)經(jīng)費(fèi)資助項(xiàng)目(W02020052);中國(guó)博士后科學(xué)基金面上項(xiàng)目(2020M670236、2021T140075);國(guó)家自然科學(xué)基金青年項(xiàng)目(81803963)