Infections Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
Infections Department, Beijing Hospital of Traditional Chinese Medicine Shunyi Branch, Beijing 101300, China.
J Tradit Chin Med. 2022 Dec;42(6):940-947. doi: 10.19852/j.cnki.jtcm.2022.06.007.
To study the mechanism of Dangfei Liganning capsule in the treatment of rats with metabolic associated fatty liver disease (MAFLD).
Totally 48 specific pathogen free Sprague-Dawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg·d respectively by gavage, Essentiale group was given 0.123 g·kg·d by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase (ALT), alanine aminotransferase (AST), triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), total protein (TP), albumin (Alb), globulin (GLB), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were measured. The levels of liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and liver pathology [hematoxylin and eosin (HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α (LXRα), steroid regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction.
From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning high-dose group was slower than all other groups. There was no significant difference in ALB level in all groups ( 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group (0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS mRNA and protein were significantly decreased (0.01).
Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning high-dose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.
研究当归六黄宁胶囊治疗代谢相关脂肪性肝病(MAFLD)大鼠的作用机制。
48 只雄性 SPF 级 SD 大鼠随机分为正常组、模型组、当归六黄宁高、中、低剂量组和易善复组,给予高脂饲料喂养 8 周,同时灌胃和造模。当归六黄宁高、中、低剂量组分别灌胃 0.27、0.135 和 0.0675 g·kg·d,易善复组灌胃 0.123 g·kg·d,正常组和模型组给予等体积蒸馏水灌胃。分别于第 0 周、第 2 周、第 4 周、第 6 周和第 8 周末称重,第 8 周末处死大鼠。检测血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(CHO)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白(LDL-C)、总蛋白(TP)、白蛋白(Alb)、球蛋白(GLB)、总胆红素(TBIL)、直接胆红素(DBIL)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平。检测肝组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和肝病理[苏木精和伊红(HE)染色、油红 O 染色]。采用免疫组化、Western blot 和逆转录-聚合酶链反应(逆转录-聚合酶链反应)检测肝 X 受体α(LXRα)、固醇调节元件结合蛋白-1(SREBP-1)和脂肪酸合酶(FAS)的表达水平。
从第 1 周到第 8 周,当归六黄宁高剂量组大鼠体重增长率均较其他各组慢。各组 ALB 水平无明显差异(0.05)。与模型组相比,当归六黄宁高剂量组 ALT、AST、LDL-C、TG、CHO、TP、GLB、TBIL、DBIL、IL-6、TNF-α水平明显降低,HDL-C 水平明显升高(0.01,<0.05)。HE 和油红 O 染色显示,大鼠肝脂肪病变减轻,LXRα、SREBP-1、FASmRNA 和蛋白表达明显降低(0.01)。
当归六黄宁胶囊能减缓 MAFLD 大鼠体重增加,降低 MAFLD 大鼠转氨酶、血脂和炎症因子水平,促进肝蛋白合成和胆汁代谢,改善 MAFLD 大鼠肝脂肪病变,其中高剂量组作用更为明显。其作用机制可能是通过阻断 LXR-SREBP-1-FAS 信号通路。