Jiang Qing-Fang, Huang Min-Yi, Wu Kang-Yuan, Weng Jie-Ling, Deng Rong-Gui, Xu Xin-Jie, Xu Jian-Pei, Jiang Tao
Department of Pharmacy, West Hospital District, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510280, China.
Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, China.
Pharmacogn Mag. 2017 Jul-Sep;13(51):430-438. doi: 10.4103/pm.pm_424_16. Epub 2017 Jul 19.
Statins cannot be used for some active liver diseases, which limits its application to some extent. The combined use of statins with other drugs may be one of the ways to solve this dilemma.
This research aims to evaluate the effects of atorvastatin combined with saponins (PNS) on rats with atherosclerosis (AS) complicated with hepatic injury.
Seventy-two male Wistar rats were randomly categorized into control group (without any intervention, Group A) and AS model groups, which were divided into hepatic injury (Groups B-E) and nonhepatic injury (Groups F-I) groups. Hepatic and nonhepatic injury groups were intragastrically treated with 5.5 mg/kg·d atorvastatin (Group B, F), 200 mg/kg·d PNS (Group C, G), 5.5 mg/kg·d atorvastatin + 200 mg/kg·d PNS (Group D, H), and normal saline (Group E, I). After 8 weeks, total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol, low density lipoprotein-cholesterol (LDL-C), and serum calcium were analyzed to evaluate the hypolipidemic effect. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and r-glutamyltransferase levels were measured to assess liver function. The thoracic aortas were used for hematoxylin-eosin staining.
In both hepatic injury and nonhepatic injury groups, TC, TG and LDL-C levels significantly decreased in Groups B, D, F, and H. ALT and AST levels significantly increased in Group B, but significantly decreased in Groups C and D. The aortic intima thickness was significantly lower in Groups B, D, F, and H than that in the normal saline group.
The combination of atorvastatin and PNS treatment showed a significant hypolipidemic effect and hepatic enzyme stability function.
The single use of saponins (PNS) in the rat model for atherosclerosis significantly reduced Ca content in serum, whereas the effect of lowing total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) is not apparent, especially as compared with atorvastatin treatmentPNS combined with atorvastatin treatment of the rat model for atherosclerosis displayed a noticeable, synergistic effect that allowed for better reduction of TC, TG, LDL-C and Ca in the serum than that with the single use of PNS or atorvastatinIn the rat liver injury combined with atherosclerosis model, the single use of PNS significantly improved liver function, whereas atorvastatin alone only aggravated liver injury in the rat model. The effect of PNS combined with atorvastatin on liver function was significantly better than that of atorvastatin aloneThe combined use of PNS and atorvastatin showed good stability of liver function on the liver injury combined with atherosclerosis model. PNS: saponins; AS: Atherosclerosis; TC: Total cholesterol; TG: Triglyceride; HDL-C: High density lipoprotein-cholesterol; LDL-C: Low density lipoprotein-cholesterol; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; T-BIL: Total bilirubin; r-GT: R-glutamyltransferase; HE: Hematoxylin-eosin.
他汀类药物不适用于某些活动性肝病，这在一定程度上限制了其应用。他汀类药物与其他药物联合使用可能是解决这一困境的方法之一。
本研究旨在评估阿托伐他汀联合三七总皂苷（PNS）对动脉粥样硬化（AS）合并肝损伤大鼠的影响。
将72只雄性Wistar大鼠随机分为对照组（未进行任何干预，A组）和AS模型组，后者又分为肝损伤组（B - E组）和非肝损伤组（F - I组）。肝损伤组和非肝损伤组分别给予5.5 mg/kg·d阿托伐他汀灌胃（B组、F组）、200 mg/kg·d PNS灌胃（C组、G组）、5.5 mg/kg·d阿托伐他汀 + 200 mg/kg·d PNS灌胃（D组、H组）以及生理盐水灌胃（E组、I组）。8周后，分析总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇（LDL - C）和血清钙，以评估降脂效果。检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶、总胆红素和γ - 谷氨酰转移酶水平，以评估肝功能。取胸主动脉进行苏木精 - 伊红染色。
在肝损伤组和非肝损伤组中，B组、D组、F组和H组的TC、TG和LDL - C水平均显著降低。B组的ALT和AST水平显著升高，但C组和D组显著降低。B组、D组、F组和H组的主动脉内膜厚度显著低于生理盐水组。
阿托伐他汀与PNS联合治疗具有显著的降脂作用和肝酶稳定功能。
在大鼠动脉粥样硬化模型中，单独使用三七总皂苷（PNS）可显著降低血清钙含量，而降低总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL - C）的效果不明显，尤其是与阿托伐他汀治疗相比。PNS联合阿托伐他汀治疗大鼠动脉粥样硬化模型显示出显著的协同作用，与单独使用PNS或阿托伐他汀相比，能更好地降低血清中的TC、TG、LDL - C和钙。在大鼠肝损伤合并动脉粥样硬化模型中，单独使用PNS可显著改善肝功能，而单独使用阿托伐他汀只会加重大鼠模型的肝损伤。PNS联合阿托伐他汀对肝功能的影响明显优于单独使用阿托伐他汀。PNS与阿托伐他汀联合使用在肝损伤合并动脉粥样硬化模型中显示出良好的肝功能稳定性。PNS：三七总皂苷；AS：动脉粥样硬化；TC：总胆固醇；TG：甘油三酯；HDL - C：高密度脂蛋白胆固醇；LDL - C：低密度脂蛋白胆固醇；ALT：丙氨酸氨基转移酶；AST：天冬氨酸氨基转移酶；ALP：碱性磷酸酶；T - BIL：总胆红素；r - GT：γ - 谷氨酰转移酶；HE：苏木精 - 伊红
