丹参多酚酸盐对肝纤维化小鼠Notch-Hes1信号通路的影响

Effects of salvianolate on Notch-Hes1 signal pathway in mice with liver fibrosis

目的 研究丹参多酚酸盐对四氯化碳(CCl_(4))致肝纤维化小鼠的保护作用及其对Notch-Hes1信号通路的影响。方法 50只小鼠按照体质量随机分为正常组、模型组、对照组和低、高剂量实验组,每组10只。模型组、对照组和低、高剂量实验组小鼠腹腔注射40%CCl_(4)橄榄油溶液3 mL·kg^(-1)建立肝纤维化模型,然后低、高剂量实验组小鼠分别按26和52 mg·kg^(-1)的剂量灌胃给予丹参多酚酸盐;对照组小鼠按0.4 mg·kg^(-1)的剂量灌胃给予秋水仙碱;正常组和模型组灌胃给予等量0.9%NaCl,每天1次,连续28 d。用酶联免疫吸附实验法检测血清谷丙转氨酶(GPT)和谷草转氨酶(GOT)水平,用实时荧光聚合酶链反应法检测肝Notch1、Jagged1和Hes1基因的表达水平。结果 低、高剂量实验组和对照组、模型组、正常组的GPT含量(28.13±6.26),(27.40±6.25),(27.23±3.09),(78.22±12.16)和(27.08±3.40)U·L^(-1),GOT含量分别为(32.96±11.14),(29.08±9.34),(30.98±7.38),(59.47±8.26)和(35.16±3.43)U·L^(-1),Notch1基因相对表达水平分别为0.31±0.04,0.28±0.30,0.49±0.04,1.62±0.03和1.00±0.00,Jagged1基因相对表达水平分别为0.98±0.04,0.96±0.03,1.02±0.04,1.49±0.04和1.00±0.00,Hes1基因相对表达水平分别为1.59±0.04,1.32±0.03,1.67±0.04,1.82±0.03和1.00±0.00。低、高剂量实验组和对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论 丹参多酚酸盐对CCl_(4)致肝纤维化小鼠具有保护作用,其机制可能与抑制Notch-Hes1信号通路有关。

Objective To study the protective effect of salvianolate on carbon tetrachloride(CCl_(4)) induced hepatic fibrosis mice and its impact on Notch-Hes1 signal pathway. Methods Totally 50 healthy mice were randomly divided into normal, model, control and experimental-L,-H groups with 10 rats per group. 3 mL·kg;40%CCl_(4)was injected to induce liver fibrosis in the mice of model, control and experimental-L,-H groups. Mice were administered with normal saline respectively in normal and model groups. Control group were administered with 0.4 mg·kg^(-1)colchicine by gastrogavage. Experimental-L,-H groups were administered with salvianolate(26 and 52 mg·kg^(-1)) by gastrogavage, once daily for 28 consecutive days. Enzyme linked immunosorbent assay was used to detect the contents of glutamic-pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT). Quantitative real-time-polymerase chain reaction was used to determine the mRNA levels of Notch1,Jagged1 and Hes1 of mice in each group. Results The GPT levels in experimental-L,-H, control, model and normal groups were( 28. 13 ± 6. 26),( 27. 40 ± 6. 25),( 27. 23 ± 3. 09),( 78. 22 ± 12. 16) and( 27. 08 ± 3. 40) U·L^(-1),GOT were( 32. 96 ± 11. 14),( 29. 08 ± 9. 34),( 30. 98 ± 7. 38),( 59. 47 ± 8. 26) and( 35. 16 ± 3. 43) U·L^(-1),the relative expression levels of Notch1 gene were0. 31 ± 0. 04,0. 28 ± 0. 30,0. 49 ± 0. 04,1. 62 ± 0. 03 and 1. 00 ± 0. 00,the relative expression levels of Jagged1gene were 0. 98 ± 0. 04,0. 96 ± 0. 03,1. 02 ± 0. 04,1. 49 ± 0. 04 and 1. 00 ± 0. 00,the relative expression levels of Hes1 gene were 1. 59 ± 0. 04,1. 32 ± 0. 03,1. 67 ± 0. 04,1. 82 ± 0. 03 and 1. 00 ± 0. 00,respectively. Compared between model and normal,experimental-L,-H groups,the differences of the factors were significant( all P < 0. 05). Conclusion Salvianolate has the protective effect on hepatic fibrosis mice induced by CCl_(4),and its mechanism was related to the inhibition of Notch-Hes1 signal pathway.