基于NF-κB/Bcl-2细胞凋亡通路探讨健脾通络解毒法对临床PLGC病变的作用影响研究
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摘要
慢性萎缩性胃炎(Chronic Atrophic Gastritis,CAG)及胃癌前病变(Precan-cerous lesions of gastric cancer, PLGC)在我国人群临床发病率高,它需经过一个漫长的、多阶段、多基因的变异积累过程而发展成胃癌。目前“正常胃黏膜→浅表性胃炎→萎缩性胃炎、肠上皮化生→不典型增生→胃癌(肠型)”的病变模式被广泛接受。中医药治疗PLGC具有可靠的疗效和较大优势,积极有效地开展对PLGC的干预阻断(二级预防)对胃癌的防治具有重要意义。
在导师姚乃礼主任医师指导下,经课题组长期研究,认为“脾虚毒损络阻”是PLGC的基本病机,以“健脾通络解毒”为本病的基本治则,可明显改善患者临床症状,并对病理组织学有一定的减缓逆转作用。针对本病设立健脾通络解毒法基础方,其主要由太子参、白术、茯苓、莪术、藤梨根、白花蛇舌草、浙贝母、甘草等组成。太子参、白术、茯苓、甘草健脾益气,莪术、活血祛瘀通络消积,藤梨根、白花蛇舌草、浙贝母解毒化痰散结,上药配伍,共奏“健脾益气、活血通络、消积解毒”之功。经前期临床观察表明,该法不但能明显改善PLGC患者临床症状,还能促进部分患者胃黏膜病变的镜下及病理向愈,在临床上取得较好的疗效。
研究目的
观察健脾通络解毒法干预PLGC的临床疗效；探讨健脾通络解毒法对PLGC细胞凋亡的影响作用；重点揭示健脾通络解毒法通过调控NF-κB> Bcl-2、Bax等分子、蛋白靶点对PLGC细胞凋亡的影响作用机制；分析PLGC证候相关因素与细胞凋亡及NF-κB、Bcl-2、Bax等指标之间的相关性。
研究方法：
本研究主要包括临床病例观察及实验研究两个部分。依据临床诊断及纳入标准入组40例PLGC患者,予健脾通络解毒方药干预治疗6个月,应用免疫组化、RT-PCR、原位末端标记法(TUNWL)等技术,检测治疗前后组织病理变化,细胞凋亡指数,凋亡信号通路(NF-κB/Bcl-2)上相关基因、蛋白表达(Bcl-2、Bax、NF-κB)等指标的变化；制定临床病例观察表,采集PLGC患者治疗前后症状变化及内镜下表现,进行统计分析,探讨其疗效以及证候相关因素,与组织病理、细胞凋亡等各指标间的相关性。
研究结果
1.临床症状：患者经健脾通络解毒法治疗6个月后,临床主症、次症及总体症状积分有明显下降(P<0.01)。主要症状明显改善以胃脘痞满为主,胃脘疼痛和情志症状积分也明显改善。患者从首诊到疗后第3个月总体症状积分减少,其改善的幅度有46.6%左右,第6个月患者总体症状积分改善的幅度有69%左右。
2.证候因素：依据患者临床四诊信息,40例PLGC患者主要的证侯因素分布以气虚、气滞、血瘀、湿、毒、气郁等为主。其中,气虚占97.5%-100%、气滞占95%-97.5%、血瘀占97.5%-100%、湿占55%-70%、毒占17.5%-47.5%、气郁占25%-40%。经健脾通络解毒法治疗后“毒”这个证候因素所占比例有明显下降,患者的舌象、脉象、胃镜下黏膜征象等均有明显改善。
3.胃镜下表现：患者的胃镜下黏膜萎缩比例在经过6个月治疗后均较明显改善；疗前有7例患者胃镜下黏膜萎缩比例达到Ⅲ级(占22.2%),疗后病患在胃镜下黏膜萎缩达到Ⅲ级的未见。入组病例治疗前后胃镜下征象积分变化明显,胃窦小弯和胃角均侧变化为著,经统计学分析均存在显著性差异(P<0.01)。
4.病理组织学：入组病例治疗前后病理积分有明显变化,以胃窦小弯部位为著,其经统计学分析,存在显著性差异(P<0.01)。胃窦加上胃角的疗前疗后胃镜下征象积分有明显降低,(P<0.05)。患者治疗前后病理萎缩及肠化所占比例均有明显变化,治疗前萎缩程度有16例重度(占44.4%)、肠化程度有23例重度(占63.9%),而治疗后萎缩程度有4例重度(占11.1%)、肠化程度有13例重度(占36.1%)。疗前有17例患者存在轻度不典型增生(占47.2%),疗后则不典型增生患者下降到5例(占13.9%)。
5.免疫组化蛋白表达：经健脾通络解毒法治疗后,NF-κB阳性表达率降为80.6%、Bcl-2阳性表达率降为50%、Bax阳性表达率略为升高86.6%。经统计分析,治疗前后NF-κB积分与Bcl-2积分有明显变化,二者均存在治疗前后的差异,NF-κB (P<0.01)、Bcl-2(P<0.01), Bax积分有略升高变化,但无显著性差异(P>0.05)。
6.细胞凋亡指数(TUNEL法)：经健脾通络解毒法治疗后细胞凋亡指数(AI)值较治疗前有减低变化,但经统计学分析,二者无显著性差异(P>0.05)。
7. RT-PCR mRNA表达：Bcl-2mRNA转录水平在治疗前表达为0.27±0.18,治疗6个月后Bcl-2mRNA转录水平表达为0.18±0.12,数值有所减低,经统计学分析,两者之间有显著性差异(P<0.05)。
8.证候因素与各指标间关系：与免疫组化指标间关系如下：①NF-κB在气虚、气滞、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异明显,具有显著统计学意义(P<0.01)；在毒这个证候因素中,治疗前后的阳性表达比率差异也具有统计学意义(P<0.05)。②Bcl-2在气虚、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异明显,具有显著统计学意义(P<0.01)；在气滞证候因素中,治疗前后的阳性表达比率差异也具有统计学意义(P<0.05)；而在“毒”证候因素中,治疗前后的阳性表达比率差异无统计学意义(P>0.05)。③Bax在气虚、气滞、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异无统计学意义(P>0.05)；在毒证候因素中,治疗前后的阳性表达比率差异具有统计学意义(P<0.05)。
9.证候类型与免疫组化指标间关系：脾胃虚弱、脾胃湿热、胃络瘀阻证型中NF-κB、Bcl-2的阳性表达比率在治疗前后存在明显差异,具有显著的统计学意义(P<0.01),在肝胃不和中NF-κB、Bcl-2的阳性表达比率在治疗前后存在差异,具有统计学意义(P<0.05)。另外,Bax在肝胃不和中的阳性表达比率在治疗前后存在差异,具有统计学意义(P<0.05)；但是在脾胃虚弱、脾胃湿热、胃络瘀阻证型中,对治疗前后Bax的阳性表达比率进行比较,其差异无统计学意义(P>0.05)。
研究结论：1.纳入的PLGC患者证候因素特点与“脾虚毒损络阻”的核心病机一致。2.“健脾通络解毒法”能够显著改善PLGC患者的主要临床症状,提高患者的生存质量。3.“健脾通络解毒法”可以明显改善PLGC患者胃黏膜萎缩、肠化、不典型增生等组织病理变化。从观察病例分析判断,该方有逆转胃癌前病变不典型增生的作用。4.“健脾通络解毒法”及其方药可通过促进细胞凋亡而对CAG伴肠上皮化生(IM)或伴有不典型增生(Dys)起到一定的治疗作用,从而达到预防PLGC向GC发展的作用。5.“健脾通络解毒法”及其方药可通过调节NF-κB来降低胃黏膜细胞内的Bcl-2含量,并调控Bcl-2与Bax的比值,从而可能有效抑制胃黏膜细胞的增殖,导致Dys等有害细胞凋亡的增强。
In our population, Chronic Atrophic Gastritis (C AG) and Precan-cerous Lesions of Gastric Cancer (PLGC) are Clinical high incidence rate, they develop to gastric cancer by going through a lengthy, multi-stage, and multi-gene mutation accumulation. At present, this mode "NGM→CSG→CAG、IM→dys→CG (intestinal)" has been widely accepted. Chinese medicine treatment of PLGC has a large advantage, actively and effectively carry out PLGC interference blocking (secondary prevention), that is important prevention of gastric cancer. Of Traditional Chinese Medicine in Treating the PLGC has reliable efficacy and a clear advantage.
Under the guidance of my professor, long-term study, he thinks "pixu luozu dusun" that is basic pathogenesis of PLGC, the basic rule of Chinese medicine treatment "Jianpi tongluo jiedu "is to obtain reliable results in clinical."Jianpi tongluo jiedu " composition has taizishan, shengbaizhu, fuling, erzhu, tengligen, baihuasheshecao, zhebeimu, gancao, etc... Taizishan、shengbaizhu、fuling、gancao can help people to tonify spleen qi, tengligen、baihuasheshecao、zhebeimu can phlegm Detoxification, upon of those components show "jianpi yiq、huoxue tongluo、xiaocheng jiedu". Early observations show that the agent not only can obviously improve PLGC patients clinical symptoms, also can promote the microscopically and part of the gastric mucosa lesion in patients with pathologic to heal. All parties reflected "jianpi tongluo jiedu" treatment principle obtains the good curative effect in clinic.
Purpose:The observed "Jianpi tongluo jiedu " intervenes of the PLGC the clinical efficacy; The explored "Jian pi tongluo jiedu " impacts on of PLGC cells apoptosis; The revealed "Jianpi tongluo jiedu " by regulating the expression of Bcl-2, Bax, NF-kappaB molecules are such as protein targets PLGC apoptosis mechanism; analysis the PLGC syndromes of the correlation is between the relevant factors, apoptosis, Bcl-2, Bax, NF-kappaB and other indicators.
Method:Into the group of40PLGC patients based on clinical diagnosis and inclusion criteria had to treatment them by "Jianpi tongluo jiedu "(taizisen、fuling、baizhu. danshenerzhu、tengligen、etc..) to interference in the six months. By immunohistochemistry, RT-PCR, in situ end labeling (TUNEL) method technology, they could detect histopathological changes, apoptotic index (AI), apoptosis signaling pathway (NF-κB/Bcl-2) gene and protein expression before and after treatment (Bcl-2, Bax, NF-κB) and other indicators of change; acquisition the PLGC patients before and after treatment had to change in symptoms and endoscopic features, sta-tistical analysis, to investigate the efficacy and syndromes related factors, and pathological, apoptosis the correlation between in each index.
Result:(1) Symptoms:In this study said "Jianpi tongluo jiedu" method after treatment, the overall primary symptom, syndrome and symptom integral were significantly lowered (P<0.01). Patients with "Jianpi tongluo jiedu" method has to treatment after six months, main symptoms improved significantly with the diagnosis the new full is given priority to, the diagnosis of pain and symptoms of modern integral were also improved significantly. From first diagnosis to the patients3months after treatment, the overall symptom score has to improvement rate of about46.6%. From first diagnosis to the patients6months after treatment, the overall symptom score has to improve the rate of about69%.
(2) Syndrome factors:According to clinical at four diagnostic information,40cases of PLGC patients mainly evidence syndrome factor distribution to qi deficiency, qi stagnation, blood stasis, dampness, poison, qi depression, etc. Among them, the qi deficiency of97.5%～100%, and the qi stagnation of95%～97.5%, blood stasis97.5%～100%, moisture55%～70%, poison17.5%～47.5%, qi depression25%～40%. After treatment with "Jianpi tongluo jiedu" method, he proportion of "poison" the syndrome factors had obvious drop, in patients with tongue, pulse condition, such as mucosa under gastroscope signs were obviously improved.
(3) Gastroscope:Gastroscopy in patients with mucosa under gastroscope contraction ratio after6months after treatment were obviously improved; There are7patients before treatment mucosa under gastroscope contraction ratio reached Ⅲ level (22.2%), patients after treatment under gastroscope mucosa atrophy Ⅲ level not seen. Into the group of cases before and after treatment under gastroscope signs integral change obviously, gastric antrum and angle of the stomach have the lateral changes, there were significantly lowered (P<0.01).
(4) Pathology:Into the group of cases the pathological integral before and after the treatment had obvious changes, in gastric antrum is little part, after statistics analysis, there were significantly lowered (P<0.01). Gastric antrum and angle of stomach before treatment after treatment under gastroscope signs integra were significantly lowered,(P<0.05). Before and after treatment in patients with pathological atrophy and intestinal proportion had the obvious change, shrinking degree before treatment there were16cases of severe (44.4%), intestinal degree of23cases of severe (63.9%), and there were4cases of severe atrophy after treatment (11.1%), intestinal degree there are13cases of severe (36.1%). There were17patients before treatment with mild atypical hyperplasia (47.2%), after treatment the patients with atypical hyperplasia were reduced to5cases (13.9%).
(5) Immunohistochemical expression:After treatment with "Jianpi tongluo jiedu" method, the nf-kappa B positive expression rate dropped to80.6%, the Bel-2positive expression rate dropped to50%, Bax positive expression rate of slightly higher86.6%. Through statistical analysis, before and after treatment the nf-kappa B integral with the Bcl-2points have obvious changes, both exist differences before and after treatment, the nf-kappa B was significantly lowered (P<0.01), the Bcl-2was significantly lowered (P <0.01), Bax integral rise slightly change, but there was no significant difference (P>0.05).
(6) Apoptosis index (TUNEL method):After treatment with "Jianpi tongluo jiedu" method apoptosis index (AI) decrease compared with before treatment, but after statistics analysis, there was no significant difference between to them (P>0.05).
(7) Rt-pcr mRNA expression:the Bcl-2expression mRNA transcription level before treatment was0.27±0.18. After6months treatment, the Bcl-2expression mRNA transcription level was0.18±0.12,there were significant differences (P<0.05).
(8) Syndrome factors relationship between with immunohistochemistry:(1) the nf-kappa B in qi deficiency, and qi stagnation, blood stasis and dampness syndrome factors of patients, the positive expression rate of difference before and after the treatment, there were significantly lowered (P<0.01); In the poison the syndrome factors, the positive expression rate of difference before and after the treatment was significantly lowered (P<0.05).(2) the Bcl-2within the qi deficiency, blood stasis and dampness syndrome factors of patients, the positive expression rate of difference before and after the treatment, there were significantly lowered (P<0.01); In and qi stagnation syndrome factors, the positive expression rate of difference before and after the treatment were significantly lowered (P<0.05); In the "poison" syndrome factor, there was no statistically significant difference of positive expression ratio before and after the treatment (P>0.05).(Bax in qi deficiency, and qi stagnation, blood stasis and dampness syndrome factors of patients, there was no statistically significant difference of positive expression ratio before and after the treatment (P>0.05); In poisonous syndrome factors, the positive expression rate of difference before and after the treatment with statistical significance (P<0.05).
(9) Symptoms relationship between with immunohistochemical:"Piweixuluo","piweishire","weiluoyuzu" had nf-kappa B and Bcl-2positive expression difference before and after therapy, there were significantly lowered (P<0.01). In "gangweibuhe" with the nf-kappa B, the Bcl-2in the positive expression rate in the differences before and after treatment, there were significantly lowered (P<0.05). Additionally, Bax in "gangweibuhe" had positive expression ratio in the differences between of before and after treatment, there were significantly lowered (P<0.05); But in "Piweixuluo","piweishire","weiluoyuzu" the positive expression of Bax ratio before and after treatment were compared, the difference is not significant (P>0.05).
Conclusion:1. The syndrome factors of PLGC patients characteristics and "Pixu luozu dusun " were at the core of the pathogenesis.2."Jianpi tongluo jiedu "could significantly improve the main clinical symptoms of PLGC patients, also improve patient's quality of life.3."Jianpi tongluo jiedu" could be obviously improved gastric mucosal atrophy, intestinal PLGC patients and atypical hyperplasia tissue pathological changes. Judging from observation cases analysis, the party had a reverse pathological changing before gastric carcinoma atypical hyperplasia.4."Jianpi tongluo jiedu" could be by promoting apoptosis in the CAG with IM or accompanied by Dys achieve in a therapeutic effect; therefore reaching the role could help patients to prevention of PLGC to GC.5."Jianpi tongluo jiedu" and its syndromes could be reduced by adjusting nf-kappa B, Bcl-2contents in gastric mucosa cells. They also could regulate the Bcl-2and the ratio of Bax, which could effectively inhibit gastric mucosa cell proliferation and apoptosis in Dys and other harmful enhancement.
在导师姚乃礼主任医师指导下,经课题组长期研究,认为“脾虚毒损络阻”是PLGC的基本病机,以“健脾通络解毒”为本病的基本治则,可明显改善患者临床症状,并对病理组织学有一定的减缓逆转作用。针对本病设立健脾通络解毒法基础方,其主要由太子参、白术、茯苓、莪术、藤梨根、白花蛇舌草、浙贝母、甘草等组成。太子参、白术、茯苓、甘草健脾益气,莪术、活血祛瘀通络消积,藤梨根、白花蛇舌草、浙贝母解毒化痰散结,上药配伍,共奏“健脾益气、活血通络、消积解毒”之功。经前期临床观察表明,该法不但能明显改善PLGC患者临床症状,还能促进部分患者胃黏膜病变的镜下及病理向愈,在临床上取得较好的疗效。
研究目的
观察健脾通络解毒法干预PLGC的临床疗效；探讨健脾通络解毒法对PLGC细胞凋亡的影响作用；重点揭示健脾通络解毒法通过调控NF-κB> Bcl-2、Bax等分子、蛋白靶点对PLGC细胞凋亡的影响作用机制；分析PLGC证候相关因素与细胞凋亡及NF-κB、Bcl-2、Bax等指标之间的相关性。
研究方法：
本研究主要包括临床病例观察及实验研究两个部分。依据临床诊断及纳入标准入组40例PLGC患者,予健脾通络解毒方药干预治疗6个月,应用免疫组化、RT-PCR、原位末端标记法(TUNWL)等技术,检测治疗前后组织病理变化,细胞凋亡指数,凋亡信号通路(NF-κB/Bcl-2)上相关基因、蛋白表达(Bcl-2、Bax、NF-κB)等指标的变化；制定临床病例观察表,采集PLGC患者治疗前后症状变化及内镜下表现,进行统计分析,探讨其疗效以及证候相关因素,与组织病理、细胞凋亡等各指标间的相关性。
研究结果
1.临床症状：患者经健脾通络解毒法治疗6个月后,临床主症、次症及总体症状积分有明显下降(P<0.01)。主要症状明显改善以胃脘痞满为主,胃脘疼痛和情志症状积分也明显改善。患者从首诊到疗后第3个月总体症状积分减少,其改善的幅度有46.6%左右,第6个月患者总体症状积分改善的幅度有69%左右。
2.证候因素：依据患者临床四诊信息,40例PLGC患者主要的证侯因素分布以气虚、气滞、血瘀、湿、毒、气郁等为主。其中,气虚占97.5%-100%、气滞占95%-97.5%、血瘀占97.5%-100%、湿占55%-70%、毒占17.5%-47.5%、气郁占25%-40%。经健脾通络解毒法治疗后“毒”这个证候因素所占比例有明显下降,患者的舌象、脉象、胃镜下黏膜征象等均有明显改善。
3.胃镜下表现：患者的胃镜下黏膜萎缩比例在经过6个月治疗后均较明显改善；疗前有7例患者胃镜下黏膜萎缩比例达到Ⅲ级(占22.2%),疗后病患在胃镜下黏膜萎缩达到Ⅲ级的未见。入组病例治疗前后胃镜下征象积分变化明显,胃窦小弯和胃角均侧变化为著,经统计学分析均存在显著性差异(P<0.01)。
4.病理组织学：入组病例治疗前后病理积分有明显变化,以胃窦小弯部位为著,其经统计学分析,存在显著性差异(P<0.01)。胃窦加上胃角的疗前疗后胃镜下征象积分有明显降低,(P<0.05)。患者治疗前后病理萎缩及肠化所占比例均有明显变化,治疗前萎缩程度有16例重度(占44.4%)、肠化程度有23例重度(占63.9%),而治疗后萎缩程度有4例重度(占11.1%)、肠化程度有13例重度(占36.1%)。疗前有17例患者存在轻度不典型增生(占47.2%),疗后则不典型增生患者下降到5例(占13.9%)。
5.免疫组化蛋白表达：经健脾通络解毒法治疗后,NF-κB阳性表达率降为80.6%、Bcl-2阳性表达率降为50%、Bax阳性表达率略为升高86.6%。经统计分析,治疗前后NF-κB积分与Bcl-2积分有明显变化,二者均存在治疗前后的差异,NF-κB (P<0.01)、Bcl-2(P<0.01), Bax积分有略升高变化,但无显著性差异(P>0.05)。
6.细胞凋亡指数(TUNEL法)：经健脾通络解毒法治疗后细胞凋亡指数(AI)值较治疗前有减低变化,但经统计学分析,二者无显著性差异(P>0.05)。
7. RT-PCR mRNA表达：Bcl-2mRNA转录水平在治疗前表达为0.27±0.18,治疗6个月后Bcl-2mRNA转录水平表达为0.18±0.12,数值有所减低,经统计学分析,两者之间有显著性差异(P<0.05)。
8.证候因素与各指标间关系：与免疫组化指标间关系如下：①NF-κB在气虚、气滞、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异明显,具有显著统计学意义(P<0.01)；在毒这个证候因素中,治疗前后的阳性表达比率差异也具有统计学意义(P<0.05)。②Bcl-2在气虚、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异明显,具有显著统计学意义(P<0.01)；在气滞证候因素中,治疗前后的阳性表达比率差异也具有统计学意义(P<0.05)；而在“毒”证候因素中,治疗前后的阳性表达比率差异无统计学意义(P>0.05)。③Bax在气虚、气滞、血瘀、内湿证候因素患者中,治疗前后的阳性表达比率差异无统计学意义(P>0.05)；在毒证候因素中,治疗前后的阳性表达比率差异具有统计学意义(P<0.05)。
9.证候类型与免疫组化指标间关系：脾胃虚弱、脾胃湿热、胃络瘀阻证型中NF-κB、Bcl-2的阳性表达比率在治疗前后存在明显差异,具有显著的统计学意义(P<0.01),在肝胃不和中NF-κB、Bcl-2的阳性表达比率在治疗前后存在差异,具有统计学意义(P<0.05)。另外,Bax在肝胃不和中的阳性表达比率在治疗前后存在差异,具有统计学意义(P<0.05)；但是在脾胃虚弱、脾胃湿热、胃络瘀阻证型中,对治疗前后Bax的阳性表达比率进行比较,其差异无统计学意义(P>0.05)。
研究结论：1.纳入的PLGC患者证候因素特点与“脾虚毒损络阻”的核心病机一致。2.“健脾通络解毒法”能够显著改善PLGC患者的主要临床症状,提高患者的生存质量。3.“健脾通络解毒法”可以明显改善PLGC患者胃黏膜萎缩、肠化、不典型增生等组织病理变化。从观察病例分析判断,该方有逆转胃癌前病变不典型增生的作用。4.“健脾通络解毒法”及其方药可通过促进细胞凋亡而对CAG伴肠上皮化生(IM)或伴有不典型增生(Dys)起到一定的治疗作用,从而达到预防PLGC向GC发展的作用。5.“健脾通络解毒法”及其方药可通过调节NF-κB来降低胃黏膜细胞内的Bcl-2含量,并调控Bcl-2与Bax的比值,从而可能有效抑制胃黏膜细胞的增殖,导致Dys等有害细胞凋亡的增强。
In our population, Chronic Atrophic Gastritis (C AG) and Precan-cerous Lesions of Gastric Cancer (PLGC) are Clinical high incidence rate, they develop to gastric cancer by going through a lengthy, multi-stage, and multi-gene mutation accumulation. At present, this mode "NGM→CSG→CAG、IM→dys→CG (intestinal)" has been widely accepted. Chinese medicine treatment of PLGC has a large advantage, actively and effectively carry out PLGC interference blocking (secondary prevention), that is important prevention of gastric cancer. Of Traditional Chinese Medicine in Treating the PLGC has reliable efficacy and a clear advantage.
Under the guidance of my professor, long-term study, he thinks "pixu luozu dusun" that is basic pathogenesis of PLGC, the basic rule of Chinese medicine treatment "Jianpi tongluo jiedu "is to obtain reliable results in clinical."Jianpi tongluo jiedu " composition has taizishan, shengbaizhu, fuling, erzhu, tengligen, baihuasheshecao, zhebeimu, gancao, etc... Taizishan、shengbaizhu、fuling、gancao can help people to tonify spleen qi, tengligen、baihuasheshecao、zhebeimu can phlegm Detoxification, upon of those components show "jianpi yiq、huoxue tongluo、xiaocheng jiedu". Early observations show that the agent not only can obviously improve PLGC patients clinical symptoms, also can promote the microscopically and part of the gastric mucosa lesion in patients with pathologic to heal. All parties reflected "jianpi tongluo jiedu" treatment principle obtains the good curative effect in clinic.
Purpose:The observed "Jianpi tongluo jiedu " intervenes of the PLGC the clinical efficacy; The explored "Jian pi tongluo jiedu " impacts on of PLGC cells apoptosis; The revealed "Jianpi tongluo jiedu " by regulating the expression of Bcl-2, Bax, NF-kappaB molecules are such as protein targets PLGC apoptosis mechanism; analysis the PLGC syndromes of the correlation is between the relevant factors, apoptosis, Bcl-2, Bax, NF-kappaB and other indicators.
Method:Into the group of40PLGC patients based on clinical diagnosis and inclusion criteria had to treatment them by "Jianpi tongluo jiedu "(taizisen、fuling、baizhu. danshenerzhu、tengligen、etc..) to interference in the six months. By immunohistochemistry, RT-PCR, in situ end labeling (TUNEL) method technology, they could detect histopathological changes, apoptotic index (AI), apoptosis signaling pathway (NF-κB/Bcl-2) gene and protein expression before and after treatment (Bcl-2, Bax, NF-κB) and other indicators of change; acquisition the PLGC patients before and after treatment had to change in symptoms and endoscopic features, sta-tistical analysis, to investigate the efficacy and syndromes related factors, and pathological, apoptosis the correlation between in each index.
Result:(1) Symptoms:In this study said "Jianpi tongluo jiedu" method after treatment, the overall primary symptom, syndrome and symptom integral were significantly lowered (P<0.01). Patients with "Jianpi tongluo jiedu" method has to treatment after six months, main symptoms improved significantly with the diagnosis the new full is given priority to, the diagnosis of pain and symptoms of modern integral were also improved significantly. From first diagnosis to the patients3months after treatment, the overall symptom score has to improvement rate of about46.6%. From first diagnosis to the patients6months after treatment, the overall symptom score has to improve the rate of about69%.
(2) Syndrome factors:According to clinical at four diagnostic information,40cases of PLGC patients mainly evidence syndrome factor distribution to qi deficiency, qi stagnation, blood stasis, dampness, poison, qi depression, etc. Among them, the qi deficiency of97.5%～100%, and the qi stagnation of95%～97.5%, blood stasis97.5%～100%, moisture55%～70%, poison17.5%～47.5%, qi depression25%～40%. After treatment with "Jianpi tongluo jiedu" method, he proportion of "poison" the syndrome factors had obvious drop, in patients with tongue, pulse condition, such as mucosa under gastroscope signs were obviously improved.
(3) Gastroscope:Gastroscopy in patients with mucosa under gastroscope contraction ratio after6months after treatment were obviously improved; There are7patients before treatment mucosa under gastroscope contraction ratio reached Ⅲ level (22.2%), patients after treatment under gastroscope mucosa atrophy Ⅲ level not seen. Into the group of cases before and after treatment under gastroscope signs integral change obviously, gastric antrum and angle of the stomach have the lateral changes, there were significantly lowered (P<0.01).
(4) Pathology:Into the group of cases the pathological integral before and after the treatment had obvious changes, in gastric antrum is little part, after statistics analysis, there were significantly lowered (P<0.01). Gastric antrum and angle of stomach before treatment after treatment under gastroscope signs integra were significantly lowered,(P<0.05). Before and after treatment in patients with pathological atrophy and intestinal proportion had the obvious change, shrinking degree before treatment there were16cases of severe (44.4%), intestinal degree of23cases of severe (63.9%), and there were4cases of severe atrophy after treatment (11.1%), intestinal degree there are13cases of severe (36.1%). There were17patients before treatment with mild atypical hyperplasia (47.2%), after treatment the patients with atypical hyperplasia were reduced to5cases (13.9%).
(5) Immunohistochemical expression:After treatment with "Jianpi tongluo jiedu" method, the nf-kappa B positive expression rate dropped to80.6%, the Bel-2positive expression rate dropped to50%, Bax positive expression rate of slightly higher86.6%. Through statistical analysis, before and after treatment the nf-kappa B integral with the Bcl-2points have obvious changes, both exist differences before and after treatment, the nf-kappa B was significantly lowered (P<0.01), the Bcl-2was significantly lowered (P <0.01), Bax integral rise slightly change, but there was no significant difference (P>0.05).
(6) Apoptosis index (TUNEL method):After treatment with "Jianpi tongluo jiedu" method apoptosis index (AI) decrease compared with before treatment, but after statistics analysis, there was no significant difference between to them (P>0.05).
(7) Rt-pcr mRNA expression:the Bcl-2expression mRNA transcription level before treatment was0.27±0.18. After6months treatment, the Bcl-2expression mRNA transcription level was0.18±0.12,there were significant differences (P<0.05).
(8) Syndrome factors relationship between with immunohistochemistry:(1) the nf-kappa B in qi deficiency, and qi stagnation, blood stasis and dampness syndrome factors of patients, the positive expression rate of difference before and after the treatment, there were significantly lowered (P<0.01); In the poison the syndrome factors, the positive expression rate of difference before and after the treatment was significantly lowered (P<0.05).(2) the Bcl-2within the qi deficiency, blood stasis and dampness syndrome factors of patients, the positive expression rate of difference before and after the treatment, there were significantly lowered (P<0.01); In and qi stagnation syndrome factors, the positive expression rate of difference before and after the treatment were significantly lowered (P<0.05); In the "poison" syndrome factor, there was no statistically significant difference of positive expression ratio before and after the treatment (P>0.05).(Bax in qi deficiency, and qi stagnation, blood stasis and dampness syndrome factors of patients, there was no statistically significant difference of positive expression ratio before and after the treatment (P>0.05); In poisonous syndrome factors, the positive expression rate of difference before and after the treatment with statistical significance (P<0.05).
(9) Symptoms relationship between with immunohistochemical:"Piweixuluo","piweishire","weiluoyuzu" had nf-kappa B and Bcl-2positive expression difference before and after therapy, there were significantly lowered (P<0.01). In "gangweibuhe" with the nf-kappa B, the Bcl-2in the positive expression rate in the differences before and after treatment, there were significantly lowered (P<0.05). Additionally, Bax in "gangweibuhe" had positive expression ratio in the differences between of before and after treatment, there were significantly lowered (P<0.05); But in "Piweixuluo","piweishire","weiluoyuzu" the positive expression of Bax ratio before and after treatment were compared, the difference is not significant (P>0.05).
Conclusion:1. The syndrome factors of PLGC patients characteristics and "Pixu luozu dusun " were at the core of the pathogenesis.2."Jianpi tongluo jiedu "could significantly improve the main clinical symptoms of PLGC patients, also improve patient's quality of life.3."Jianpi tongluo jiedu" could be obviously improved gastric mucosal atrophy, intestinal PLGC patients and atypical hyperplasia tissue pathological changes. Judging from observation cases analysis, the party had a reverse pathological changing before gastric carcinoma atypical hyperplasia.4."Jianpi tongluo jiedu" could be by promoting apoptosis in the CAG with IM or accompanied by Dys achieve in a therapeutic effect; therefore reaching the role could help patients to prevention of PLGC to GC.5."Jianpi tongluo jiedu" and its syndromes could be reduced by adjusting nf-kappa B, Bcl-2contents in gastric mucosa cells. They also could regulate the Bcl-2and the ratio of Bax, which could effectively inhibit gastric mucosa cell proliferation and apoptosis in Dys and other harmful enhancement.
引文
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