【作者】 王恬；

【导师】 冯义朝；

【作者基本信息】 延安大学 ， 内科学， 2010， 硕士

【摘要】 目的应用免疫组化法(SABC法)检测胃蛋白酶原C(PGC)在单纯浅表性胃炎、单纯萎缩性胃炎、伴肠化、伴异型增生、胃癌各组中的表达情况;同一组病例中Hp(+)病例在根治前后PGC的表达情况;应用ELISA法检测以上各组血清sPGC、sPGA浓度及Hp(+)病例在根治前后血清sPG浓度;分析胃蛋白酶原与幽门螺杆菌的关系;分析PGC表达水平与血清sPGC、sPGA的相关性,给临床工作提供更有益的信息,进一步诠释胃蛋白酶原作为胃癌标志物在诊治中的应用意义。方法利用延安大学附属医院病理科2008-2009年胃镜及手术活检标本, 49例单纯浅表性胃炎、35例单纯萎缩性胃炎、40例伴肠化、39例伴异型增生、41例腺癌;采用SABC法检测各组胃黏膜PGC表达情况;ELISA法检测血清sPGC、sPGA值,对实验所得结果采用SPSS16.0统计软件包进行统计学处理,计数资料采用χ2检验进行分析,计量资料采用t检验、方差分析;组织表达与血清含量相关性采用Pearson相关性分析;P<0.05有统计学意义。结果1. PGC在各种胃疾病黏膜组织中的表达PGC在不同胃疾病黏膜中的表达有差异(P=0.000):在单纯浅表性胃炎(95.9%)、单纯萎缩性胃炎(77.1%)、伴肠化(55.0%)、伴异型增生(51.3%)、腺癌(7.3%)中PGC阳性率呈现递减。单纯浅表组与其余各组相比阳性率差异有统计学意义(P值均小于0.05);伴肠化与伴异型增生组相比,差异无统计学意义(P=0.741);单纯萎缩与肠化/异型增生、胃癌PGC阳性率比较差异有统计学意义(P值均小于0.05);肠化/异型增生与胃癌PGC阳性率有显著差异(P值均小于0.05)。2.各种胃疾病患者的PG血清浓度比较本组实验测得sPGC、sPGA浓度在各组间比较差异有统计学意义(Pa=0.000 Pc=0.000)。sPGA在浅表组与其余各组相比呈现递减,差异有统计学意义(P值均小于0.05) ;萎缩组与其余各组相比差异有统计学意义(P值均小于0.05) ;肠化组与异型增生组相比差异无统计学意义(P=0.264);肠化组/异型增生组与胃癌组比较差异有统计学意义(P值均小于0.05);sPGC从单纯浅表-单纯萎缩-伴肠化/异性增生-胃癌,sPGC浓度也表现为逐渐上降趋势,总体上各组sPGC浓度差异有统计学差异(P<0.05),胃癌组与其他各组相比差异显著(P值均小于0.05),但其余组间相互比较差异无统计学意义(P值均大于0.05)。3. PGC不同组织表达与血清PG浓度的比较从浅表-萎缩-肠化-异型增生-胃癌,随粘膜病变程度加深,组织PGC表达与血清sPGA呈负相关、与sPGC呈正相(ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007)。4.在Hp(+)组与(-)组的PGC表达情况和sPGC/sPGA血清学比较PGC表达在Hp(+)组和(-)组间比较差异有统计学意义(P<0.05),在单纯萎缩组、伴肠化组、伴异型增生组PGC表达率在Hp(+)组显著低于Hp(-)组(P值均小于0.05),但在单纯浅表组二者差异无统计学意义(P=1.000)。在根除成功组不同胃疾病黏膜PGC表达率表现为明显的上升趋势,但在单纯浅表组和单纯萎缩组,差异无统计学意义,而伴肠化组、伴异型增生组则差异显著(各组P值依次为1.000,0.242,0.024,0.030)。根除失败组,PGC表达率未见明显变化,差异无统计学意义,(各组P值分别为0.271,1.000,1.000,1.000)。血清PG值在Hp(+)组和(-)组浓度比较差异显著(P值均小于0.05);sPGA仅在单纯浅表组的Hp(+)组∕Hp(-)组相比有统计学意义(P=0.000),在其余组的Hp(+)组∕Hp(-)组相比无显著意义(P值均大于0.05);sPGC在各组的Hp(+)组∕Hp(-)组相比差异有统计学意义(P值均小于0.05)。根除成功组血清sPGA、sPGC值在治疗前后比较有统计学意义(P值均小于0.05);根除失败组sPGC、sPGA值在治疗前后相比差异无统计学意义(P值均大于0.05);结论1. PGC表达在不同年龄、性别的胃疾病患者中无显著差异;sPGA、sPGC在男性高于女性,65岁以上患者的血清PG值普遍低于65岁以下患者;2. PGC在不同胃疾病黏膜中的动态表达呈逐渐降低的趋势,提示胃黏膜细胞恶性表达与PGC抗原表达呈负相关,提示这个指标与胃疾病的发生发展有良好的相关性;3.血清sPGA明显降低则胃癌危险性增高,提示血清PG降低可能与胃癌的发生发展有关;4.单独应用sPGA或者sPGC进行胃黏膜疾病的检测,临床意义不显著。但若同时进行血清PG值及PGC抗原表达率检测,二具者有良好的相关性,可作为临床筛查胃癌及癌前疾病的指标;5. Hp阳性伴有PGC阴性表达和低sPGA、高sPGC的患者胃疾病恶性程度高,应密切随访;6. Hp根治成功后血清PG值显著下降; PGC表达在根治前后的肠化组、异型增生组有显著差异,提示Hp根除可以使PGC表达率增加,或许可以减慢肠化、异型增生这些癌前病变向胃癌的发展速度。更多还原

【Abstract】 Objective Immunohistochemical method(SABC) was used to detect the expression levels of PGC in CSG,CAG,IM,DYS and GC tissue, variation in the same group before and after radical cure for Hp infection. To detect the level of sPGA, sPGC and the variation in serum pepsinogen concentration before and after Helicobacter pylori eradication by ELISA. To analyze the relationship between the PGC and Hp, the correlation between the expression of PGC and the level of sPGA, sPGC, which will help to guidance the clinical work , also further interpreted PGC may be a good molecular maker for the early diagnosis of gastric carcinoma .Method The experiment was performed from 2008 to 2009 at the Department of Pathology in Affiliated Hospital of Medical College of Yan’an University . The expression of PGC was detected by immunohistochemistry in 49 chronic superficial gastritis(CSG), 35 chronic atrophic gastritis (CAG), 40intestinal metaplasia(IM), 39 Dysplasia (DYS)and 41gastric cancer (Ca) in 204 endoscopic biopsy specimens. To detect the level of sPGA, sPGC by ELISA. The data were analyzed for significance using the statistical software SPSS 16.0 computer package. Chi-square test was used in the analysis of enumeration data, the differences of measurement data were compared with the analysis of variance and t test, Tissue expression and serum in correlation analysis using Person. P <0.05 statistically significant.Result1. PGC Expression among different gastric disease tissue there were differences in PGC Expression among different gastric disease tissue, the expression of pepsinogenC decreased significantly on sequence(P<0.05 ).the positive rate of PGC is 95.9%,77.1%,55.0%,51.3%,7.3% (CSG,CAG, IM,DYS,Ca). The positive rate of PGC in CSG was significantly higher than in the others(P<0.05), The positive rate was significantly higher in CAG than in IM,DYS and Ca, but there is no significant difference between IM and DYS(P>0.05). The positive rate was significantly lower in Ca than in others(P<0.05).2. Comparison Serum Pepsinogen Levels in patients with different gastric diseasesThere were differences in concentration of sPGA, sPGC among the groups. And there was extreme significant statistics difference (P< 0.05). sPGA decreased significantly on sequence(P<0.05). sPGC increased significantly on sequence(P<0.05).sPGC in Ca is higher than in others(P<0.05),but no significant difference in serum PGC were detected in CSG,CAG, IM,DYS(P>0.05).3. Comparisons between different expression of tissue PGC and concentration of serum PGBy the decrease of PGC expression, lesion tissue in CAG,CSG,IM,DYS,Ca, their concentration of serum PGC was increased and their sPGA concentration was decreased, and there is statistic difference(P<0.05). The sPGA decreased, the sPGC increased along with decrease of PGC expression in lesion tissue, they have good relativity and the statistic difference was similar (ra=0.956,Pa= 0.011;rc=-0.968,Pc=0.007).4. Comparisons between different expression of tissue PGC and concenrtation of serum PG in H.p infections and non-infectionsRate of PGC expression in groups (CSG,IM,DYS,Ca) of H.p infection was lower than that of non-infection(P<0.05),but there is no statistic difference in CAG(P>0.05). The rate of PGC increased significantly on sequence in different groups of eradication successfully (P<0.05),and in IM,DYS,there is statistic difference(P<0.05), but in CAG or CSG, there is no difference(P>0.05). The difference was not statistically significant in the gruoups of eradication failure (P>0.05).Concentration of sPGA, sPGC in groups of H.p infection was higher than that of non-infection (P<0.05). There is significantly difference of sPGC among the gruoups (P<0.05).but, only in CAG there is significantly difference of sPGA(P<0.05). Concentration of sPGA, sPGC is lower in different groups of eradication successfully than before (P<0.05), but the difference was not statistically significant in the gruoups of eradication failure (P>0.05).Conclusion1. the rate of PGC expression in different age and sex of gastric disease in patients with no significant differences. sPGA and sPGC is higher in male than in female, is higher in <65 guoups than in≥65 groups.2. Tissue expression of PGC is negative to the malignant degree of gastric mucosa cell and positive with the development of gastric of gastric mucosa diseases.3. Serum sPGA decreased obviously is an increased risk.4. The test, which only use sPGA or sPGC to detect gastric mucosa, isn’t a marked in clinic, and at the same time the detection of sPG is relative to the tissue expression of PGC antigen, it is a convenient, economic maker to screen and diagnose gastric mucosa disease, and has some clinical value.5. the patients with H.p infection ,low sPGA or high sPGC and negative expression of PGC should be closely followed.6. Concentration of sPGA, sPGC is lower of eradication successfully than before (P<0.05).The rate of PGC increased significantly on sequence of eradication successfully in IM, DYS(P<0.05). It shows Hp perhaps can slow IM, DYS of these premalignant changes to the development of cancer.更多还原