目的 探討注射用丹參多酚酸（SAFI）對(duì)CCl₄所致大鼠肝損傷的改善情況。方法 將50只ip 20% CCl₄造成化學(xué)性肝損傷模型的SD大鼠隨機(jī)分為模型組（ig 0.9%氯化鈉注射液＋尾iv 0.9%氯化鈉注射液）、水飛薊賓膠囊（SFJ，陽性藥，37.8 mg·kg⁻¹，ig給藥＋尾iv 0.9%氯化鈉注射液）組和SAFI低、中、高劑量（5.805、11.610、23.220 mg·kg⁻¹，尾iv給藥＋ig 0.9%氯化鈉注射液）組，每組10只，另取10只大鼠作為對(duì)照組（ig 0.9%氯化鈉注射液＋尾iv 0.9%氯化鈉注射液）。每天給藥1次，連續(xù)給藥14 d。每天給藥后觀察各組大鼠生存狀態(tài)；給藥結(jié)束后處死取材，酶聯(lián)免疫吸附（ELISA）試劑盒法檢測大鼠血清中丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶AST）、白蛋白（ALB）水平，以及大鼠肝組織中基質(zhì)金屬蛋白酶（MMP）、層黏蛋白（LN）、透明質(zhì)酸（HA）、白細(xì)胞介素6（IL-6）、白細(xì)胞介素1β（IL-1β）、腫瘤壞死因子α（TNF-α）、α-平滑肌肌動(dòng)蛋白（α-SMA）、白細(xì)胞介素10（IL-10）、丙二醛（MDA）、超氧化物歧化酶（SOD）、Ⅰ型膠原蛋白（COLⅠ）、Ⅲ型膠原蛋白（COLⅢ）水平；采用Western blotting法檢測各組大鼠肝組織中α-SMA、COLⅠ、COLⅢ的表達(dá)；取肝組織進(jìn)行HE染色觀察病理變化。結(jié)果 與模型組相比，各給藥組大鼠精神狀態(tài)明顯好轉(zhuǎn)，SFJ組和SAFI中、高劑量組肝指數(shù)顯著下降（P＜0.05、0.01）；各給藥組血清中ALT、AST水平顯著降低，ALB水平顯著升高（P＜0.05、0.01、0.001）；肝組織中肝損傷指標(biāo)MMP水平顯著升高，HA、LN水平顯著降低（P＜0.01、0.001）；膠原蛋白相關(guān)因子α-SMA、COLⅠ、COLⅢ水平顯著降低，炎癥因子TNF-α、IL-6、IL-1β水平顯著降低，IL-10水平顯著升高（P＜0.05、0.01、0.001）；Western blotting結(jié)果顯示，與模型組比較，SFJ組和SAFI中劑量組α-SMA、COLI、COLⅢ蛋白表達(dá)顯著降低（P＜0.01、0.001）；HE染色顯示，各給藥組與模型組相比，炎癥細(xì)胞浸潤情況有所緩解，病理損害情況明顯減輕。結(jié)論 SAFI通過抗脂質(zhì)過氧化反應(yīng)、有效改善細(xì)胞外基質(zhì)（ECM）沉積、積極促進(jìn)膠原蛋白降解、抑制結(jié)締組織增生，同時(shí)可以緩解大鼠炎癥反應(yīng)，從而改善肝損傷，降低肝纖維化的風(fēng)險(xiǎn)。

Objective To investigate the effect of Salvianolic Acids for Injection (SAFI) on CCl₄-induced liver injury in rats. MethodsFifty SD rats with chemical liver injury induced by intraperitoneal injection of 20% CCl₄ were randomly divided into model group (ig 0.9% sodium chloride injection + tail iv 0.9 % sodium chloride injection), SAFI-low, medium, high dose group (5.805, 11.610, and 23.22 mg·kg⁻¹, tail iv + ig 0.9 % sodium chloride injection), Shuifeijibin capsule (SFJ) group (37.8 mg·kg⁻¹, ig + tail iv 0.9% sodium chloride injection). Another 10 SD rats were taken as the normal group (tail iv + ig 0.9 % sodium chloride injection). After continuous administration for 14 days, the survival status of rats in each group was observed after daily administration. After the end of administration, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) in serum and matrix metalloproteinase (MMP), laminin (LN), hyaluronic acid (HA), interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), α-smooth muscle actin (α-SMA), interleukin 10 (IL-10), malondialdehyde (MDA), superoxide dismutase (SOD), type I collagen (COLI), type III collagen (COLIII) in liver tissue were detected by enzyme-linked immunosorbent assay (ELISA) kit. The expression of α-SMA, COLI and COLIII in liver tissue of rats in each group was detected by Western blotting. The pathological changes of liver tissue were observed by HE staining. Results Compared with the model group, the mental state of rats in each drug administration group was significantly improved. The liver index of the SFJ group and the medium and high-dose SAFI groups decreased significantly (P < 0.05, 0.01). The levels of ALT and AST in the serum of each drug administration group decreased significantly, and the level of ALB increased significantly (P < 0.05, 0.01, 0.001). The level of MMP in liver tissue was significantly increased, and the levels of HA and LN were significantly decreased (P < 0.01, 0.001). The levels of collagen-related factors α-SMA, COLI and COLIII were significantly decreased, and the levels of inflammatory factors TNF-α, IL-6, and IL-1β decreased significantly, while the level of IL-10 increased significantly (P < 0.05, 0.01, 0.001). Western blotting results showed that compared with the model group, the protein expressions of α-SMA, COLI, and COLⅢ in the SFJ group and the medium-dose SAFI group decreased significantly (P < 0.01, 0.001). HE staining showed that compared with the model group, the infiltration of inflammatory cells in each drug administration group was alleviated, and the pathological damage was significantly reduced. Conclusion SAFI can improve liver injury and reduce the risk of liver fibrosis by inhibiting lipid peroxidation, effectively improving extracellular matrix (ECM) deposition, actively promoting collagen degradation, inhibiting connective tissue proliferation, and alleviating inflammation in rats.

R285.5

天津市制造業(yè)高質(zhì)量發(fā)展專項(xiàng)資金—天津天士力之驕藥業(yè)有限公司技術(shù)中心創(chuàng)新能力建設(shè)（ZZY20232088）