目的 探讨在已有肝损伤的情况下，注射用丹参多酚酸（SAFI）与3种他汀类药物联合使用对大鼠肝脏损伤安全性的影响。方法 采用20% CCl₄油溶液ip建立大鼠肝损伤模型，将造模成功的大鼠随机分为8组：模型组（ig＋尾iv 0.9%氯化钠注射液）、SAFI组（ig 0.9%氯化钠注射液＋尾iv SAFI 11.61 mg·kg⁻¹）、阿托伐他汀组（ig阿托伐他汀钙片1.79 mg·kg⁻¹＋尾iv 0.9%氯化钠注射液）、瑞舒伐他汀组（ig瑞舒托伐他汀钙片1.79 mg·kg⁻¹＋尾iv 0.9%氯化钠注射液）、普伐他汀组（ig普伐他汀钠片1.79 mg·kg⁻¹＋尾iv 0.9%氯化钠注射液）、阿托伐他汀＋SAFI组（ig阿托伐他汀钙片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹）、瑞舒伐他汀＋SAFI组（ig瑞舒伐他汀钙片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹）、普伐他汀＋SAFI组（ig普伐他汀钠片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹），另取10只大鼠为对照组（ig＋尾iv 0.9%氯化钠注射液），各组每天给药1次，持续14 d。给药结束后各组大鼠腹主动脉取血，试剂盒法检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）水平；取出全部肝组织称质量，计算肝指数，试剂盒法检测肝组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6、IL-10水平；HE染色后对肝组织进行病理学观察。结果 与模型组比较，给药后SAFI组肝指数显著降低（P＜0.05）；各给药组血清ALT水平显著降低（P＜0.01、0.001），瑞舒伐他汀组、普伐他汀组、阿托伐他汀＋SAFI组、瑞舒伐他汀＋SAFI组、普伐他汀＋SAFI组、SAFI组血清AST、LDH水平显著降低（P＜0.01、0.001），肝组织SOD水平显著升高（P＜0.001）；瑞舒伐他汀组、普伐他汀组、瑞舒伐他汀＋SAFI组、普伐他汀＋SAFI组、SAFI组血清ALP水平显著降低（P＜0.01、0.001），肝组织TNF-α水平显著降低，IL-10水平显著升高（P＜0.05、0.01、0.001）；各给药组肝组织MDA、IL-1β、IL-6水平显著降低（P＜0.05、0.01、0.001），瑞舒伐他汀组、阿托伐他汀＋SAFI组、瑞舒伐他汀＋SAFI组、普伐他汀＋SAFI组肝组织GSH-Px水平显著升高（P＜0.05、0.01、0.001）。与他汀类药物单用组比较，阿托伐他汀＋SAFI组血清AST、LDH显著降低（P＜0.01），肝组织SOD水平显著升高（P＜0.01）；瑞舒伐他汀＋SAFI组肝组织MDA水平显著降低（P＜0.05）；普伐他汀＋SAFI组肝组织GSH-Px水平显著升高（P＜0.05）；各联用组肝组织TNF-α、IL-1β、IL-6均有降低趋势，但差异无统计学意义。HE染色结果显示，各给药组均未发现肝损伤加重的情况。结论 在已有肝损伤的情况下，注射用SAFI与他汀类药物联合使用对肝脏的安全性良好，并未出现损伤加重的现象，且均表现出改善肝损伤作用。

Objective To investigate the effect of Salvianolic Acids for Injection (SAFI) combined with three statins on liver safety in rats with liver injury.Methods The rat model of liver injury was established by intraperitoneal injection of 20 % CCl₄ oil solution. The successfully modeled rats were randomly divided into eight groups: model group (ig + tail iv 0.9% sodium chloride injection), SAFI group (ig 0.9% sodium chloride injection + tail iv SAFI 11.61 mg·kg⁻¹), atorvastatin group (ig atorvastatin calcium tablets 1.79 mg·kg ⁻¹ + tail iv 0.9 % sodium chloride injection), rosuvastatin group (ig rosuvastatin calcium tablets 1.79 mg·kg⁻¹ + tail iv 0.9 % sodium chloride injection), pravastatin group (ig pravastatin sodium tablets 1.79 mg·kg⁻¹ + tail iv 0.9 % sodium chloride injection), atorvastatin + SAFI group (ig atorvastatin calcium tablets 1.79 mg·kg⁻¹ + tail iv SAFI 11.61 mg·kg⁻¹), rosuvastatin + SAFI group (ig rosuvastatin calcium tablets 1.79 mg·kg⁻¹ + tail iv SAFI 11.61 mg·kg⁻¹), pravastatin + SAFI group (ig pravastatin sodium tablets 1.79 mg·kg⁻¹ + tail iv SAFI mg·kg⁻¹), and another 10 rats were taken as control group (ig + tail iv 0.9 % sodium chloride injection). Each group was administered once a day for 14 days. After the end of administration, blood was taken from the abdominal aorta of rats in each group, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum were detected by kit method. All liver tissues were taken out and weighed to calculate the liver index. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-10 (IL-10) in liver tissues were detected by kit method. HE pathological observation of liver tissue. Results Compared with the model group, the liver index of the SAFI group was significantly decreased after administration (P < 0.05). The levels of serum ALT in each administration group were significantly decreased (P < 0.01, 0.001). The levels of serum AST and LDH in rosuvastatin group, pravastatin group, atorvastatin + SAFI group, rosuvastatin + SAFI group, pravastatin + SAFI group and SAFI group were significantly decreased (P < 0.01, 0.001), and the level of SOD in liver tissue was significantly increased (P < 0.001). The levels of serum ALP in rosuvastatin group, pravastatin group, rosuvastatin + SAFI group, pravastatin + SAFI group and SAFI group were significantly decreased (P < 0.01, 0.001), the level of TNF-α in liver tissue was significantly decreased, and the level of IL-10 was significantly increased (P < 0.05, 0.01, 0.001). The levels of MDA, IL-1β and IL-6 in liver tissue of each administration group were significantly decreased (P < 0.05, 0.01, 0.001). The levels of GSH-Px in liver tissue of rosuvastatin group, atorvastatin + SAFI group, rosuvastatin + SAFI group and pravastatin + SAFI group were significantly increased (P < 0.05, 0.01, 0.001). Compared with the statin group, the serum AST and LDH levels in the atorvastatin + SAFI group were significantly decreased (P < 0.01), and the SOD level in the liver tissue was significantly increased (P < 0.01). The level of MDA in liver tissue of rosuvastatin + SAFI group was significantly decreased (P < 0.05). The level of GSH-Px in liver tissue of pravastatin + SAFI group was significantly increased (P < 0.05). The levels of TNF-α, IL-1β and IL-6 in liver tissue of each combination group showed a decreasing trend, but the difference was not statistically significant. HE staining results showed that no aggravation of liver injury was found in each administration group. Conclusion In the case of liver injury, the combined use of SAFI and statins is safe for the liver, and there is no aggravation of injury.

R285.5

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）