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目的:探讨疏肝健脾方药对非酒精性脂肪性肝炎(nonalcoholic steatosis hepatitis,NASH)合并心脏舒张功能不全大鼠干预的作用机制.方法:采用高脂饲料喂养复制NASH大鼠实验模型,各药物组分别灌服疏肝方、健脾方和综合方(疏肝方和健脾方的合方)进行干预,16wk后用Visual Sonics Vevo770TM高分辨率小动物超声诊断仪检测大鼠心脏每搏输出量(SV)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)用以评价大鼠心脏收缩功能,检测E/A比值用以评价大鼠心脏舒张功能.然后处死大鼠,腹主动脉采血,用全自动生化分析仪检测血脂及肝脂的含量;常规HE染色观察肝组织病理变化;ELISA法检测血清TNF-α和IL-6的水平.结果:肝组织病理染色提示大鼠NASH造模成功;与正常对照组相比,模型组大鼠心脏舒张功能明显降低(1.59±0.24vs1.03±0.13,P<0.01),血清TNF-α和IL-6含量显著升高(13.57±4.64vs28.26±8.60;59.28±71.53vs132.81±74.22,P<0.01、0.05),血清TC、LDL及肝组织TC、TG含量也明显升高(1.42±0.29vs3.82±0.91;0.30±0.11vs0.81±0.27;0.90±0.14vs11.86±1.29;0.75±0.38vs6.17±1.83,均P<0.01),SV、LVEF、LVFS均比正常组有不同程度的下降;各药物组大鼠心脏舒张功能较模型组有显著改善,以健脾高剂量组、综合方高剂量组的E/A比值升高最为明显(1.26±0.23vs1.03±0.13;1.35±0.15vs1.03±0.13,均P<0.01);各药物组大鼠血清TNF-α及IL-6含量与模型组相比明显下降,以综合方高剂量组的血清下降最为明显(15.07±6.00vs28.26±8.60;67.72±44.24vs132.81±74.22,P<0.01,0.05);脂质代谢检测以合方高剂量组的血清TG及肝组织TC、TG下降最为明显(0.45±0.14vs0.83±0.26;9.17±1.02vs11.86±1.29;2.54±0.74vs6.17±1.83,均P<0.01).结论:NASH大鼠伴有心脏舒张功能不全,疏肝健脾方药抗NASH及改善NASH大鼠心脏舒张功能可能与其降低血清中炎症因子TNF-α和IL-6的水平有关.
Objective: To explore the mechanism of Shuganjianpi Decoction on the intervention of nonalcoholic steatosis hepatitis (NASH) with cardiac dysfunction in rats.Methods: The experimental model of NASH rats was fed with high-fat diet, and each drug The rats were randomly divided into three groups: Shuganfang, Jianpifang and Fufangfang (Shuganfang and Jianpifang) respectively. After 16wk, the cardiac output of rat was measured by using Visual Sonics Vevo770TM high resolution small animal’s ultrasonic diagnostic apparatus (SV), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured to evaluate the cardiac contractile function in rats and the E / A ratio was used to evaluate the diastolic function in rats.After that, rats were sacrificed , Abdominal aorta blood samples were collected, the content of lipids and hepatic lipids were detected by automatic biochemical analyzer, the pathological changes of liver tissue were observed by routine HE staining, and the levels of serum TNF-α and IL-6 were detected by ELISA.Results: Compared with the normal control group, the cardiac diastolic function of the model group was significantly decreased (1.59 ± 0.24 vs 1.03 ± 0.13, P <0.01), and the levels of TNF-α and IL-6 in serum were significantly increased (13.57 ± 4.64 vs. 28.26 ± 8.60; 59.28 ± 71.53 vs 132.8 1 ± 74.22, P <0.01, 0.05). The contents of TC, LDL, TC and TG in liver tissue were also increased significantly (1.42 ± 0.29vs3.82 ± 0.91; 0.30 ± 0.11vs0.81 ± 0.27; 0.90 ± 0.14vs11. 86 ± 1.29; 0.75 ± 0.38vs6.17 ± 1.83, all P <0.01), while SV, LVEF and LVFS all decreased to some extents. Compared with model group, the diastolic function of each drug group was significantly improved The E / A ratio of spleen high-dose group and comprehensive-dose high-dose group was the most obvious (1.26 ± 0.23vs1.03 ± 0.13; 1.35 ± 0.15vs1.03 ± 0.13, both P <0.01) Serum levels of TNF-αand IL-6 were significantly decreased compared with the model group, and the serum of the high-dose and high-dose group decreased most significantly (15.07 ± 6.00vs28.26 ± 8.60; 67.72 ± 44.24vs132.81 ± 74.22, P <0.01 , 0.05). The decrease of serum TG, liver tissue TC and TG in the high-dose and high-dose groups of the lipid metabolism test were the most significant (0.45 ± 0.14vs0.83 ± 0.26; 9.17 ± 1.02vs11.86 ± 1.29; 2.54 ± 0.74vs6. 17 ± 1.83, P <0.01) .Conclusion: NASH rats with diastolic dysfunction, Shuganjianpi Decoction anti-NASH and improve the diastolic function of NASH rats may be associated with its lower serum levels of inflammatory cytokines TNF- and IL- 6 level related.