[关键词]
[摘要]
目的 探讨注射用丹参多酚酸(SAFI)对CCl4所致大鼠肝损伤的改善情况。方法 将50只ip 20% CCl4造成化学性肝损伤模型的SD大鼠随机分为模型组(ig 0.9%氯化钠注射液+尾iv 0.9%氯化钠注射液)、水飞蓟宾胶囊(SFJ,阳性药,37.8 mg·kg−1,ig给药+尾iv 0.9%氯化钠注射液)组和SAFI低、中、高剂量(5.805、11.610、23.220 mg·kg−1,尾iv给药+ig 0.9%氯化钠注射液)组,每组10只,另取10只大鼠作为对照组(ig 0.9%氯化钠注射液+尾iv 0.9%氯化钠注射液)。每天给药1次,连续给药14 d。每天给药后观察各组大鼠生存状态;给药结束后处死取材,酶联免疫吸附(ELISA)试剂盒法检测大鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶AST)、白蛋白(ALB)水平,以及大鼠肝组织中基质金属蛋白酶(MMP)、层黏蛋白(LN)、透明质酸(HA)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、α-平滑肌肌动蛋白(α-SMA)、白细胞介素10(IL-10)、丙二醛(MDA)、超氧化物歧化酶(SOD)、Ⅰ型胶原蛋白(COLⅠ)、Ⅲ型胶原蛋白(COLⅢ)水平;采用Western blotting法检测各组大鼠肝组织中α-SMA、COLⅠ、COLⅢ的表达;取肝组织进行HE染色观察病理变化。结果 与模型组相比,各给药组大鼠精神状态明显好转,SFJ组和SAFI中、高剂量组肝指数显著下降(P<0.05、0.01);各给药组血清中ALT、AST水平显著降低,ALB水平显著升高(P<0.05、0.01、0.001);肝组织中肝损伤指标MMP水平显著升高,HA、LN水平显著降低(P<0.01、0.001);胶原蛋白相关因子α-SMA、COLⅠ、COLⅢ水平显著降低,炎症因子TNF-α、IL-6、IL-1β水平显著降低,IL-10水平显著升高(P<0.05、0.01、0.001);Western blotting结果显示,与模型组比较,SFJ组和SAFI中剂量组α-SMA、COLI、COLⅢ蛋白表达显著降低(P<0.01、0.001);HE染色显示,各给药组与模型组相比,炎症细胞浸润情况有所缓解,病理损害情况明显减轻。结论 SAFI通过抗脂质过氧化反应、有效改善细胞外基质(ECM)沉积、积极促进胶原蛋白降解、抑制结缔组织增生,同时可以缓解大鼠炎症反应,从而改善肝损伤,降低肝纤维化的风险。
[Key word]
[Abstract]
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.
[中图分类号]
R285.5
[基金项目]
天津市制造业高质量发展专项资金—天津天士力之骄药业有限公司技术中心创新能力建设(ZZY20232088)