健中愈疡片对胃溃疡线粒体DNA修复酶调控机制的实验与临床研究

The Clinical and Experimental Study of Adjustment of Mitochondrion DNA Repair Enzyme of Gastric Ulcer by JianZhongYuYang Tablet

目的从分子水平探讨健脾益气方药在胃溃疡黏膜损伤修复过程中对线粒体DNA修复酶的调控机制及观察愈合质量,深入探讨线粒体DNA修复酶对胃溃疡的胃黏膜的修复逆转作用及中药的作用靶点。方法用临床观察和动物实验研究健脾益气方药对胃溃疡胃黏膜的保护与修复作用。比较健中愈疡片、黏膜保护剂胃舒平以及H2受体拮抗剂法莫替丁对胃黏膜线粒体8-氧鸟嘌呤DNA糖基化酶、胸腺嘧啶乙二醇DNA糖基化酶、3-甲基腺嘌呤DNA糖基化酶的影响,并进行健脾益气方药与黏膜保护剂胃舒平以及H2受体拮抗剂法莫替丁对胃溃疡愈合质量的比较和评价。结果正常组线粒体DNA修复酶含量很低,胃溃疡组线粒体DNA修复酶含量很高,健中愈疡片组线粒体DNA修复酶含量较正常组极显著增高(P<0.01),胃舒平组线粒体DNA修复酶含量与胃溃疡组没有差异(P>0.05),法莫替丁组线粒体DNA修复酶含量比胃溃疡组减少(P<0.05)。而溃疡愈合质量则健中愈疡片组和法莫替丁组没有差异(P>0.05),二者均好于胃舒平组(P<0.05);在脾虚证的改善上,健中愈疡片组明显优于法莫替丁组和胃舒平组(P<0.01)。结论健中愈疡片对胃溃疡的治疗机理之一是对线粒体DNA修复酶进行了调控,提高了修复因素,这是其作用靶点之一;而法莫替丁和胃舒平组治疗机理分别是减少损害因素和进行物理保护,其作用与线粒体DNA修复酶关系不甚密切;但对脾虚症状的改善上,健中愈疡片的作用远远高于西药组,显示了中医药治疗的优越性。

Objective Clinical practice has proved that invigorating spleen and benefiting vital energy Chinese formulated products -Jian Zhong Yu Yang Tablet（JZYYT） has good curative effect on tough gastric ulcer. Our research is to reveal how the invigorating spleen and benefiting vital energy Chinese drugs regulate the mitochondrion DNA repair enzymes, to reveal how Chinese drugs cure gastric ulcer, and to find the target of Chinese drugs. Methods Our study was to treat gastric ulcer by invigorating spleen and benefiting vital energy Chinese drugs through clinical observation and experimental research, and compared with mucosa protectant - gastropine and H2 receptor antagonist - famotidine about the mucosa mitochondrion 8 - oxygen guanine DNA glycosylase, thymine glycol DNA glycosylase, 3 - methyl adenine DNA glycosylase, the effect of gastralgia, splenic asthenia and quality of ulcer recovery. In clinical research, we observed the rank of gastralgia, splenic asthenia and compositive therapeutic effects. In animal experiment, we detected the body weight, frequency of twisting in unit time, suspending time, index number of gastric ulcer, and microcirculation of gastric mucosa such as the value of B/（ R ＋ G ＋ B） to clarify the regulation effect of invigorating spleen and benefiting vital energy Chinese drugs on mitochondrion DNA repair enzymes, and the therapeutic effect on gastric ulcer in molecular level. Results Mitochondrion DNA repair enzymes were the lowest in the gastric mucosa of normal group, but they were very high in gastric ulcer group, there had significant difference between them（ P 〈 0.01 ） ; Mitochondrion DNA repair enzymes had no difference between gastropine group and gastric ulcer group（ P 〉 0.05 ） ; Mitochondrion DNA repair enzymes in famotidine group decreased extremely compared with gastric ulcer group（ P 〈 0.01 ）, but still extremely higher than normal group（ P 〈 0.01 ） ;Mitochondrion DNA repair enzymes were the highest in JianZhongYuYang Tablet group, and had extreme differences compared with each of the other 4 groups（ P 〈 0.01 ）. Grade of gastralgia ：before treatment , there had extreme differences between normal group and the other 4 groups（P 〈 0.01 ） ,there had no differences among the other 4 groups（ P 〉 0.05 ）. After treatment, grades of gastralgia in JianZhongYuYang Tablet group and famotidine group were the lowest, and had no difference between them （P 〉 0.05 ） ;the grade of gastralgia in gastropine group was lower, there had extreme difference compared with gastric ulcer group （P 〈 0.01 ） ,but also had extreme differences compared with JianZhongYuYang Tablet group and famotidine group. In the difference of grade of gastralgia before and after treatment, JianZhongYuYang Tablet group had no difference compared with famotidine group （ P 〉 0.05 ）, but gastropine group had obvious difference compared with JianZhongYuYang Tablet group （ P 〈 0.05 ）, and had extreme differences compared with famotidine group （P 〈 0.01 ）. Syndrome of splenic asthenia： before treatment , the rank of splenic asthenia in each group was balanced except normal group. After treatment, the change of splenic asthenia in JianZhongYuYang Tablet group was the biggest, and had extremely significant differences from the other 4 groups （P 〈 0.01 ）, famotidine group and gastropine group was extremely significant differences compared with gastric ulcer group（ P 〈0. 01 ）, but famotidine group had no difference with gastropine group（ P 〉 0.05 ）. Conclusion To treat gastric ulcer, JianZhongYuYang Tablet has excellent effect to relieve pain and to eliminate splenic asthenia. It has the same effect with famotidine to alleviate pain, but is better than western drugs in eliminating splenic asthenia and improving microcireulation of gastric mucosa. In mechanism of action, JianZhongYuYang Tablet can increase the mitochondrion DNA repair enzymes greatly to repair the damaged gastric mucosa, and promote the self - cure of gastric ulcer, this is the difference to western medicine. Western medicine emphasize the counteraction against harmful factors, while JianZhongYuYang Tablet focuses on self- repair, it is consistent with the theory of traditional Chinese medicine ＂supporting healthy energy to eliminate evils＂ , ＂if healthy energy is inside, evil factors can not come in＂. So our research give the evidence to show the superiority of Chinese drugs. We know, the function of Chinese traditional patent .drugs have muhiplicate mechanisms to cure disease, our study proved one of the targets of Chinese traditional patent drugs how to cure gastric ulcer only, that is ： Chinese traditional patent drugs can adjust mitochondrion DNA repair enzymes. With the development of molecular biology, we wish we can find more mechanisms of Chinese traditional patent drugs trough experiments in the future, and make greater contributions to the cause of investigating, developing the precious wealth - traditional Chinese medicine.