应用模糊集理论对壮肝逐瘀煎抗肝纤维化的优化研究

Optimization and study of Zhuangganzhuyujian treatment for anti-hepatic fibrosis by fuzzy set theory

目的优化壮肝逐瘀煎配伍，创制高效新方。方法SPF健康、清洁级大鼠260只，随机取15只作为正常对照组（A组）。剩余大鼠采用CCt,诱导的肝纤维化模型，于第4周末造模大鼠随机处死5只进行病理形态学检测证实造模成功后，将其余造模大鼠随机分为病理模型组（B组）、壮肝逐瘀颗粒配比1～28组、大黄蛰虫丸组（C组），每组8只，分别给予生理盐水、大黄蛰虫丸、正交设计后壮肝逐瘀1～28组灌胃。观察治疗前后大鼠血清中白介素（IL-2、6、10）及肿瘤坏死因子-α（TNF-α）；肝组织羟脯氨酸（Hyp）、过氧化物歧化酶（SOD）、丙二醛（MDA）的含量及基质金属蛋白酶（MMP-1、2、3）、基质金属蛋白酶抑制物（TIMP-1、2）mRNA的水平，通过模糊数学进行数据处理。结果在壮肝逐瘀煎颗粒各组及C组、B组中壮肝逐瘀煎颗粒第11剂量组，治疗后肝纤维化大鼠血清IL-2、IL-10、SOD水平较高，血清IL-6、TNF-α及肝组织Hyp、MDA、MMP-1，2，3水平较低。结论通过对原方剂组进行拆方后分出27个方剂组加原方组共28组，并对实验的各指标进行运算和分析后结果认为壮肝逐瘀煎配比11组（柔肝化纤颗粒）最优。

Objective To optimize the ompatibility of Zhuangganzhuyujian for making new efficient formula. Methods 260 SPF healthy rats of clean grade were selected for study, among which 15 rats were selected randomly for the control group （group A）, the other rats were made the model of hepatic fibrosis by CC14 at the fourth weekend. 5 rats from the model group were sacrificed for confirming the success of model by pathomorphology, the other model rats were divided randomly into the pathological group （group B）, Zhuangganzhuyujian group with ration from 1 to 28, Dahuang Zhechong Pill group （group C）, each group had 8 rats, and each group was given normal saline, Zhuangganzhuyujian after orthogonal design, and Dahuang Zhechong Pill by garage respectively. The serum levels of IL-2, IL-6, IL-10, tumour necrosis factor-α （TNF-α）, Hydroproxy- line （Hyp）, superoxide dismutase （SOD）, malondialdehyde （MDA）, mRNA level of matrix metalloproteinase （MMP）-1, 2, 3 and tissue inhibitor of metalloproteinase （TIMP）-1, 2 were measured and the data were analyzed by fuzzy mtthematics. Results The levels of serum IL-2, 10 and SOD in the 1 lth dosage group of Zhuangganzhuyujian after treatment were higher among those in all dosage groups of Zhuangganzhuyujian, group B and group C, while the levels of serum IL-6, TNF-α, Hyp, MDA and MMP-1, 2, 3 from liver tissue in the llth dosage group of Zhuangganzhuyujian after treatment were lower among those in groups. Conclusion The 1 lth dosage group of Zhuangganzhuyujian （Rouganhuaxian Pill） is the best formula confirmed by ex- periment after separating the former prescription to making 28 groups of formula with the former formula.