目的 探討在已有肝損傷的情況下，注射用丹參多酚酸（SAFI）與3種他汀類藥物聯(lián)合使用對大鼠肝臟損傷安全性的影響。方法 采用20% CCl₄油溶液ip建立大鼠肝損傷模型，將造模成功的大鼠隨機分為8組：模型組（ig＋尾iv 0.9%氯化鈉注射液）、SAFI組（ig 0.9%氯化鈉注射液＋尾iv SAFI 11.61 mg·kg⁻¹）、阿托伐他汀組（ig阿托伐他汀鈣片1.79 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液）、瑞舒伐他汀組（ig瑞舒托伐他汀鈣片1.79 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液）、普伐他汀組（ig普伐他汀鈉片1.79 mg·kg⁻¹＋尾iv 0.9%氯化鈉注射液）、阿托伐他?。玈AFI組（ig阿托伐他汀鈣片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹）、瑞舒伐他?。玈AFI組（ig瑞舒伐他汀鈣片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹）、普伐他?。玈AFI組（ig普伐他汀鈉片1.79 mg·kg⁻¹＋尾iv SAFI 11.61 mg·kg⁻¹），另取10只大鼠為對照組（ig＋尾iv 0.9%氯化鈉注射液），各組每天給藥1次，持續(xù)14 d。給藥結(jié)束后各組大鼠腹主動脈取血，試劑盒法檢測血清中丙氨酸氨基轉(zhuǎn)移酶（ALT）、天冬氨酸氨基轉(zhuǎn)移酶（AST）、堿性磷酸酶（ALP）、乳酸脫氫酶（LDH）水平；取出全部肝組織稱質(zhì)量，計算肝指數(shù)，試劑盒法檢測肝組織中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽過氧化物酶（GSH-Px）、腫瘤壞死因子-α（TNF-α）、白細胞介素（IL）-1β、IL-6、IL-10水平；HE染色后對肝組織進行病理學(xué)觀察。結(jié)果 與模型組比較，給藥后SAFI組肝指數(shù)顯著降低（P＜0.05）；各給藥組血清ALT水平顯著降低（P＜0.01、0.001），瑞舒伐他汀組、普伐他汀組、阿托伐他?。玈AFI組、瑞舒伐他?。玈AFI組、普伐他?。玈AFI組、SAFI組血清AST、LDH水平顯著降低（P＜0.01、0.001），肝組織SOD水平顯著升高（P＜0.001）；瑞舒伐他汀組、普伐他汀組、瑞舒伐他?。玈AFI組、普伐他?。玈AFI組、SAFI組血清ALP水平顯著降低（P＜0.01、0.001），肝組織TNF-α水平顯著降低，IL-10水平顯著升高（P＜0.05、0.01、0.001）；各給藥組肝組織MDA、IL-1β、IL-6水平顯著降低（P＜0.05、0.01、0.001），瑞舒伐他汀組、阿托伐他汀＋SAFI組、瑞舒伐他?。玈AFI組、普伐他汀＋SAFI組肝組織GSH-Px水平顯著升高（P＜0.05、0.01、0.001）。與他汀類藥物單用組比較，阿托伐他?。玈AFI組血清AST、LDH顯著降低（P＜0.01），肝組織SOD水平顯著升高（P＜0.01）；瑞舒伐他?。玈AFI組肝組織MDA水平顯著降低（P＜0.05）；普伐他?。玈AFI組肝組織GSH-Px水平顯著升高（P＜0.05）；各聯(lián)用組肝組織TNF-α、IL-1β、IL-6均有降低趨勢，但差異無統(tǒng)計學(xué)意義。HE染色結(jié)果顯示，各給藥組均未發(fā)現(xiàn)肝損傷加重的情況。結(jié)論 在已有肝損傷的情況下，注射用SAFI與他汀類藥物聯(lián)合使用對肝臟的安全性良好，并未出現(xiàn)損傷加重的現(xiàn)象，且均表現(xiàn)出改善肝損傷作用。

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

天津市制造業(yè)高質(zhì)量發(fā)展專項資金—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）