多模态超声技术评估活血化瘀法逆转大鼠早期肝硬化的实验研究

Experimental study on reversal of early liver cirrhosis by promoting blood circulation and removing blood stasis by multimodal ultrasound

关键词:  超声  早期肝硬化  逆转  扶正化瘀胶囊  血府逐瘀胶囊

Key words:  ultrasound  early liver cirrhosis  reversal  Fuzheng Huayu Capsule  Xuefu Zhuyu Capsule

摘要:

[目的] 探讨多模态超声技术在评估活血化瘀法对大鼠早期肝硬化逆转的应用价值。[方法] 39只Wistar雄性大鼠随机分为正常组和造模组，后者以0.5%二甲基亚硝胺按2 μg/g体质量腹腔注射4周复制大鼠早期肝硬化模型。造模成功后将其随机分为：模型组、扶正化瘀组（FZ组）、血府逐瘀组（XF组）、扶正+血府组（FZ+XF组），后3组分别经灌胃给药治疗4周。8周后行超声检查，观察肝实质灌注及门静脉血流等相关参数，分析各组超声参数与治疗效果的相关性。处死大鼠后，经腹主动脉取血，行血清学指标检测；取肝组织固定，行HE、Masson染色。[结果] 1）模型组大鼠门静脉内径增大、流速减慢、肝实质峰值强度降低、达峰时间增加、曲线下面积减小，血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（CⅣ）水平升高，与正常组比较均有统计学差异（P<0.05）。2）FZ组、XF组和FZ+XF组大鼠的门静脉内径减小、流速增快、肝实质峰值强度增高、达峰时间减慢、曲线下面积增大，与模型组比较均有统计学差异（P<0.05）。3）FZ+XF组的大鼠门静脉内径减小，FZ+XF组及XF组肝实质达峰时间减慢，与FZ组比较均有统计学差异（P<0.05）。4）3组治疗组的血清LN、PCⅢ、CⅣ及FZ组、FZ+XF组的血清HA水平明显降低，与模型组比较均有统计学差异（P<0.05）。5）肝实质HE及Masson染色显示，活血化瘀疗法可以改善肝细胞变性坏死、抑制胶原纤维增生、减轻肝纤维化程度。[结论] 经3组药物治疗后大鼠门静脉高压改善，肝血流灌注增加，且FZ+XF组及XF组明显优于FZ组，与病理相对照说明活血化瘀疗法有助于大鼠早期肝硬化的逆转。利用多模态超声技术评估活血化瘀疗法逆转大鼠早期肝硬化具有一定的应用价值。

Abstract:

[Objective] To explore the application value of multimodal ultrasound technology in evaluating the effect of promoting blood circulation and removing blood stasis on the reversal of early liver cirrhosis in rats. [Methods] Thirty nine Wistar male rats were randomly divided into normal group and model group. The latter was intraperitoneally injected with 0.5% dimethylnitrosamine at 2 μL/g body weight for 4 weeks to replicate the rat early liver cirrhosis model. After successful modeling,they were randomly divided into:model group,Fuzheng Huayu group (FZ group),Xuefu Zhuyu group (XF group) and Fuzheng + Xuefu group (FZ+XF group),the latter three groups were respectively treated by gavage for 4 weeks. After 8 weeks,ultrasound examination was performed to observe relevant parameters such as hepatic parenchymal perfusion and portal vein blood flow,and the correlation between the ultrasound parameters of each group and the treatment effect was analyzed. After the rats were sacrificed,blood was collected through the abdominal aorta and tested for serological indicators;liver tissues were fixed and stained with HE and Masson. [Results] 1) In the model group,the diameter of portal vein increased,the velocity of blood flow slowed down,the intensity of peak parenchyma decreased,the peak time prolonged,the area under the curve decreased,the content of serum hyaluronic acid (HA),laminin (LN),procollagen Ⅲ (PC Ⅲ) and collagen Ⅳ (C Ⅳ) increased,there was a significant difference between the model group and the control group (P<0.05). 2) In the FZ group,XF group and FZ + XF group,the internal diameter of the portal vein decreased,the flow velocity increased,the peak parenchymal intensity of the liver increased,the peak time decreased,and the area under the curve increased. Compared with the model group,there were significant differences (P<0.05). 3) The portal vein diameter of rats in the FZ + XF group decreased,and the peak time of liver parenchyma in the FZ + XF group and the XF group slowed down,which was significantly different from that in the FZ group (P<0.05). 4) The serum LN,type III procollagen,type IV collagen levels of three groups and the serum HA levels of the FZ and FZ + XF groups in the three treatment groups were significantly lower than those in the model group (P<0.05). 5) HE and Masson staining of liver parenchyma showed that the treatment of promoting blood circulation and removing blood stasis can improve the degeneration and necrosis of liver cells,inhibit the proliferation of collagen fibers,and reduce the degree of liver fibrosis. [Conclusion] After treatment with three groups of drugs,portal hypertension in rats improved and liver blood perfusion increased,and the FZ+XF and XF groups were significantly better than the FZ group. Compared with pathology,the treatment of promoting blood circulation and removing blood stasis was helpful to the early liver cirrhosis in rats. reverse. The use of multi-modal ultrasound technology to evaluate the effect of activating blood circulation and removing blood stasis on reversing early liver cirrhosis in rats has certain application value.