摘要
研究目的:
通过对Hp相关慢性胃炎、消化性溃疡脾胃湿热证患者幽门螺杆菌(Helicobacterpylori,Hp)感染、白细胞介素-8(interleukin-8,IL-8)及热休克蛋白70(heat shockprotein 70,HSP70)表达的检测,并以之与脾气虚证相对照,探讨Hp相关胃病脾胃湿热证发生的病理机制,说明不同证型具有不同的发病机制,为进一步加强脾胃湿热证的现代研究,完善脾本质的探讨,以及提高中医药治疗脾胃病的临床疗效提供依据。
研究方法:
1、选择中医辨证属于脾胃湿热证和脾气虚证的慢性胃炎、消化性溃疡患者75例,其中脾胃湿热证Hp(+)热重于湿者11例,脾胃湿热证Hp(+)湿热并重者10例,脾胃湿热证Hp(+)湿重于热者11例,脾胃湿热Hp(-)者21例,脾气虚证Hp(+)者12例,脾气虚证Hp(-)者10例。招募健康志愿者10例作为正常对照组。各组受试对象均完成临床观察表,由专人询问,对症状进行评定计分并填写表格。
2、各组受试对象均于电子胃镜下取胃窦粘膜,电子胃镜下和常规HE染色法观察胃粘膜的炎症程度。采用美蓝染色法和快速尿素酶试验法检测Hp感染,二项结果均阳性诊断为Hp阳性,二项结果均阴性诊断为Hp阴性,一阴一阳不列入本研究。
3、对各组受试对象进行临床资料的分析。
4、采用免疫组织化学标记法检测各组胃粘膜HSP70、IL-8的蛋白表达。
5、采用荧光定量PCR法检测各组胃粘膜HSP70、IL-8的mRNA表达。
研究结果:
1、各组受试对象的一般情况(性别,年龄)未见显著性差异(P＞0.05),具有可比性。各组疾病种类分布(慢性浅表性胃炎、消化性溃疡)未见显著性差异(P＞0.05),各组间具有可比性。
2、脾胃湿热证组与脾气虚证组Hp检出率经统计学分析未发现显著性差异(P＞0.05),但脾胃湿热证组Hp检出率为60.38%,脾气虚证组Hp检出率为54.55%,Hp检出率呈脾胃湿热证组＞脾气虚证组的趋势。Hp感染各组的Hp感染严重程度未发现显著性差异(P＞0.05)。
3、慢性胃炎、消化性溃疡脾胃湿热证主要临床症状积分比较,Hp阳性组与Hp阴性组未见显著性差异(P＞0.05)。
4、脾胃湿热证组炎症程度较正常对照组重(P＜0.05),较脾气虚证组有偏重的趋势(P＞0.05);同一证型中Hp感染者较非Hp感染者炎症程度重(P＜0.05)。脾胃湿热证组炎症活动程度较正常对照组重(P＜0.05),较脾气虚证组有偏重的趋势(P＞0.05);脾胃湿热证中Hp感染者较非Hp感染者炎症活动程度重(P＜0.05);脾气虚证中Hp感染者较非Hp感染者炎症活动程度有较重的趋势(P＞0.05)。Hp感染程度与胃粘膜炎症程度呈正相关(P＜0.001),相关系数为0.672;Hp感染程度与胃粘膜炎症急性活动呈正相关(P＜0.001),相关系数为0.683。
5、HSP70的表达
HSP70蛋白表达脾胃湿热证组与脾气虚证组、正常对照组比较有显著性差异(P＜0.05),脾胃湿热证组表达高。脾胃湿热Hp(+)组与脾胃湿热Hp(-)组、脾气虚Hp(-)组、正常对照组比较有显著性差异(P＜0.05),脾胃湿热Hp(+)组表达高;三组亚型与正常对照组比较均有显著性差异(P＜0.05);热重于湿组与脾气虚证Hp(+)组、脾气虚证Hp(-)组比较有显著性差异(P＜0.05),热重于湿组表达高;湿热并重组与脾气虚证Hp(-)组比较有显著性差异(P＜0.05),湿热并重组表达高;脾胃湿热Hp(-)组与正常对照组比较有显著性差异(P＜0.05),脾胃湿热Hp(-)组表达高。脾胃湿热证Hp(+)组各亚型之间无显著性差异(P＞0.05),但有热重于湿＞湿热并重＞湿重于热的趋势。脾气虚证Hp(+)组较脾气虚证Hp(-)组表达偏高,但未见显著性差异(P＞0.05)。
HSP70mRNA表达脾胃湿热证组与正常对照组比较有显著性差异(P＜0.05),脾胃湿热证组表达高。脾胃湿热Hp(+)组与正常对照组、脾胃湿热Hp(-)组、脾气虚Hp(-)组比较有显著性差异(P＜0.05),脾胃湿热Hp(+)组表达高。脾胃湿热Hp(+)热重于湿组与正常对照组、脾胃湿热Hp(-)组、脾气虚Hp(-)组比较有显著性差异(P＜0.05),热重于湿组表达高。脾胃湿热Hp(+)湿热并重组与正常对照组、脾气虚Hp(-)组比较有显著性差异(P＜0.05),湿热并重组表达高。脾气虚Hp(+)组与正常对照组比较有显著性差异(P＜0.05),脾气虚Hp(+)组表达高。脾胃湿热证组表达较脾气虚证组表达偏高,但未见显著性差异(P＞0.05)。脾胃湿热证Hp(+)组各亚型之间无显著性差异(P＞0.05),但有热重于湿＞湿热并重＞湿重于热的趋势。脾气虚证组Hp感染较非Hp感染表达偏高,但未见显著性差异(P＞0.05)。
6、IL-8的表达
IL-8蛋白表达各组间未见显著性差异(P＞0.05)。脾胃湿热证组较脾气虚证组、正常对照组有偏高的趋势,脾胃湿热证Hp感染组有热重于湿＞湿热并重＞湿重于热的趋势,Hp感染组较非Hp感染组有表达偏高的趋势。
IL-8mRNA表达脾胃湿热证组与正常对照组比较有显著性差异(P＜0.05),脾胃湿热证组表达高。脾胃湿热Hp(+)组与正常对照组、脾胃湿热Hp(-)组、脾气虚Hp(-)组比较有显著性差异(P＜0.05),脾胃湿热Hp(+)组表达高。脾胃湿热Hp(+)热重于湿组与正常对照组、脾胃湿热Hp(-)组、脾气虚Hp(-)组比较有显著性差异(P＜0.05),热重于湿组表达高。脾胃湿热Hp(+)湿热并重组与正常对照组比较有显著性差异(P＜0.05),湿热并重组表达高于正常对照组。脾胃湿热Hp(+)湿重于热组与正常对照组比较有显著性差异(P＜0.05),湿重于热组表达高于正常对照组。脾胃湿热证组表达较脾气虚证组表达偏高,但未见显著性差异(P＞0.05)。脾胃湿热证Hp(+)组各亚型之间无显著性差异(P＞0.05),但有热重于湿＞湿热并重＞湿重于热的趋势。脾气虚证组Hp感染较非Hp感染表达偏高,但未见显著性差异(P＞0.05)。
研究结论:
1、慢性胃炎、消化性溃疡患者Hp感染率呈脾胃湿热证组＞脾气虚证组的趋势;而Hp感染各组的Hp感染严重程度未发现显著性差异。
2、慢性胃炎、消化性溃疡脾胃湿热证患者临床症状积分与Hp感染未发现明显相关性,Hp感染并非是引起脾胃湿热证的决定性因素,尚有其他因素对其影响。
3、慢性胃炎、消化性溃疡患者胃粘膜炎症程度及炎症活动程度可能与证型有一定程度上的相关性,脾胃湿热证组炎症明显重于正常对照组,与脾气虚证组相比有较重的趋势。
4、慢性胃炎、消化性溃疡患者胃粘膜炎症程度及炎症的活动程度可能与Hp感染存在一定程度上的相关性,Hp感染者的炎症较重。Hp感染程度可能与胃粘膜炎症程度及炎症的活动性呈正相关,Hp感染程度越重,胃粘膜的炎症越重。
5、HSP70蛋白和mRNA表达水平呈现脾胃湿热证组＞脾气虚证组＞正常对照组的趋势;而在脾胃湿热Hp(+)组各亚型中,又呈现热重于湿＞湿热并重＞湿重于热的趋势。可提示HSP70的表达与证型可能存在着一定的相关性。HSP70以热证表达为明显,“热”与“湿”在脾胃湿热证中的比分可能会影响HSP70在脾胃湿热证中的表达水平。
6、HSP70蛋白和mRNA表达水平在脾胃湿热证组Hp感染者高于非Hp感染者,在脾气虚证组Hp感染者有较非Hp感染者表达偏高的趋势。具有胃粘膜保护作用的HSP70可能在一定程度上代表机体正气的一部分;Hp感染可加重胃粘膜的炎症反应,引起并加重胃粘膜损伤,可能在一定程度代表外来邪气的一部分。HSP70表达水平与Hp感染的关系可能部分体现了脾胃湿热证的“正邪交争”状态。
7、IL-8蛋白和mRNA表达水平呈现脾胃湿热证组＞脾气虚证组＞正常对照组的趋势;而在脾胃湿热Hp(+)组各亚型中,又呈现热重于湿＞湿热并重＞湿重于热的趋势。IL-8为一强大的中性粒细胞趋化因子,与炎症反应关系密切,IL-8的表达水平可能与证型存在着一定的相关性。
8、IL-8蛋白和mRNA表达水平呈现Hp感染组较非Hp感染组偏高的趋势。IL-8在复杂的细胞因子网络中占重要地位,可激活和趋化嗜中性粒细胞,在炎症反应中发挥重要作用,可能为脾胃湿热证Hp作用于胃粘膜的机制之一。
Aim:
By detecting the Helicobacter pylori(Hp) infection,interieukin-8(IL-8) and heat shock protein 70(HSP70) expressions of Hp-related chronic superficial gastritis(CSG) and peptic ulcer(PU) patients with splenogastric hygropyrexia syndrome,and contrast it with deficiency of spleen-QI Syndrome, to explore the pathomechanism of the Hp-related gastrosia with splenogastric hygropyrexia syndrome,to illustrate that the different type of syndrome have different pathogenesis,in order to provide the basis for further strengthen the modern research of splenogastric hygropyrexia syndrome,improve the approach to the nature of spleen,and raise the clinical therapeutic effect of traditional Chinese medicine treatment of the spleen and stomach disease.
Methods:
1.Choose 75 patients with CSG and PU,11 cases belong to the group of splenogastric hygropyrexia syndrome Hp(+) and heavy dampness impairing heat, 10 cases belong to the group of splenogastric hygropyrexia syndrome Hp(+) and simultaneous onset of dampness and heat,11 cases belong to the group of splenogastric hygropyrexia syndrome Hp(+) and heavy heat impairing dampness, 21 cases belong to the group of splenogastric hygropyrexia syndrome Hp(-),12 cases belong to the group of deficiency of spleen-QI syndrome Hp(+),and 10 cases belong to the group of deficiency of spleen-QI syndrome Hp(-).10 cases of recruitment of healthy volunteers as normal control group.Subjects in each group have completed the clinical observation of form,by the person asked to carry out assessment of symptoms score and complete the forms.
2.The tunica mucosa sinus ventriculi of all the cases were collected under the gastroscope.The inflammation of mucosa was observed by gastroscope and common hematocylin-eosin staining method.Hp was detected by toluidine blue staining method and fast urease test,two positive results were diagnosed with Hp-positive,two negative results were diagnosed with Hp-negative,one positive and the other negative results were not included in this study.
3.The clinical data of all the cases were analyzed.
4.The protein expression of HSP70 and IL-8 were detected by immunohistochemistry.
5.The mRNA expression of HSP70 and IL-8 were detected by FQ-PCR (Fluorescence Quantitive Polymerase Chain Reaction).
Results:
1.There was no ignificant difference of the general situation(gender, age)(P＞0.05),comparable in each group.There was no ignificant difference of the distribution of the type of illness(CSG,PU)(P＞0.05),comparable in each group.
2.There was no significant difference of the Hp infective rate between splenogastric hygropyrexia syndrome group and deficiency of spleen-QI syndrome group(P＞0.05).Hp infective rate of splenogastric hygropyrexia syndrome group is 60.38%.Hp infective rate of deficiency of spleen-QI syndrome group is 54.55%.The Hp detection rates had the tendency that splenogastric hygropyrexia syndrome group＞deficiency of spleen-QI syndrome group.There was no significant difference of Hp infection level in all the Hp infected groups (P＞0.05).
3.There was no significant difference in the main clinical symptom score of the CSG and PU patients with splenogastric hygropyrexia syndrome between Hp-positive group and Hp-negative group(P＞0.05).
4.The mucosa inflammation in pathology of splenogastric hygropyrexia syndrome group was more severe than the normal control group(P＜0.05),and in the same type of syndrome Hp-positive group was more severe than the Hp-negative group(P＜0.05).The mucosa inflammation activity in pathology of splenogastric hygropyrexia syndrome group was more severe than the normal control group(P＜0.05),and in splenogastric hygropyrexia syndrome Hp-positive group was more severe than the Hp-negative group(P＜0.05).
The Hp gradient of infection and gastric mucosa inflammation was positively correlated(P＜0.001),the correlation coefficient was 0.672;Hp infection and gastric mucosa with acute inflammatory activity was positively correlated(P＜0.001),the correlation coefficient was 0.683.
5.HSP70 protein expression of splenogastric hygropyrexia syndrome group was significantly higher than deficiency of spleen-QI syndrome group and the normal control group(P＜0.05).The expression of splenogastric hygropyrexia syndrome Hp(+) group was significantly higher than splenogastric hygropyrexia syndrome Hp(-) group,deficiency of spleen-Ql syndrome Hp(-) group and normal control group(P＜0.05).The expression of three sub-divided groups of splenogastric hygropyrexia syndrome were significantly higher than normal control group(P＜0.05).The heavy heat impairing dampness group was significantly higher than deficiency of spleen-QI syndrome Hp(+) and Hp(-) group(P＜0.05).The simultaneous onset of dampness and heat group was significantly higher than deficiency of spleen-Ol syndrome Hp(-) group (P＜0.05).The splenogastric hygropyrexia syndrome Hp(-) group was significantly higher than normal control group(P＜0.05).Among the three sub-divided groups of splenogastric hygropyrexia syndrome Hp(+),there was a tendency of HSP70 protein expression:heavy heat impairing dampness＞simultaneous onset of dampness and heat＞heavy dampness impairing heat,but there were no significanct difference among them(P＞0.05).
HSP70 mRNA expression of splenogastric hygropyrexia syndrome group was significantly higher than normal control group(P＜0.05).The splenogastric hygropyrexia syndrome Hp(+) group was significantly higher than splenogastric hygropyrexia syndrome Hp(-) group,deficiency of spleen-QI syndrome Hp(-) group and normal control group(P＜0.05).The heavy heat impairing dampness group was significantly higher than splenogastric hygropyrexia syndrome Hp(-) group,deficiency of spleen-QI syndrome Hp(-) group and normal control group (P＜0.05).The simultaneous onset of dampness and heat group was significantly higher than deficiency of spleen-QI syndrome Hp(-) group and normal control group(P＜0.05).The deficiency of spleen-QI syndrome Hp(+) was significantly higher than normal control group(P＜0.05).Among the three sub-divided groups of splenogastric hygropyrexia syndrome Hp(+),there was a tendency of HSP70 mRNA expression:heavy heat impairing dampness＞simultaneous onset of dampness and heat＞heavy dampness impairing heat,but there were no significant difference among them(P＞0.05).
6.IL-8 protein expression among all the groups had no significant difference(P＞0.05).There were tendencies of IL-8 protein expression: splenogastric hygropyrexia syndrome group＞deficiency of spleen-QI syndrome group＞normal control group,heavy heat impairing dampness＞simultaneous onset of dampness and heat＞heavy dampness impairing heat,Hp-positive group was higher than Hp-negative group.
IL-8 mRNA expression of splenogastric hygropyrexia syndrome group was significantly higher than normal control group(P＜0.05).The splenogastric hygropyrexia syndrome Hp(+) group was significantly higher than splenogastric hygropyrexia syndrome Hp(-) group,deficiency of spleen-QI syndrome Hp(-) group and normal control group(P＜0.05).The heavy heat impairing dampness group was significantly higher than splenogastric hygropyrexia syndrome Hp(-) group,deficiency of spleen-QI syndrome Hp(-) group and normal control group (P＜0.05).The simultaneous onset of dampness and heat group was significantly higher than normal control group(P＜0.05).The heavy dampnes impairing heat group was significantly higher than normal control group(P＜0.05).
Conclusion:
1.The Hp detection rates of CSG and PU had the tendency that splenogastric hygropyrexia syndrome group＞deficiency of spleen-QI syndrome group.There was no significant difference of Hp infection level in all the Hp infected groups.
2.Clinical symptom score and Hp infection of the CSG and PU patients with splenogastric hygropyrexia syndrome did not find significant correlation.Hp infection was not the only factor of splenogastric hygropyrexia syndrome, which also had other influencing factors.
3.The degree of the mucosa inflammation and inflammatory activity of CSG and PU patients may be related to the type of syndrome.The inflammation of splenogastric hygropyrexia syndrome group was obviously more severe than the normal control group,and compared with deficiency of spleen-QI syndrome group it had more severe tendency.
4.The degree of the mucosa inflammation and inflammatory activity of CSG and PU patients may be related to the Hp infection,Hp-positive group was more severe than the Hp-negative group.The level of Hp infection possibly positive correlated to the degree of the mucosa inflammation and inflammatory activity. The higher level of Hp infecton as while as the more severe mucosa inflammation would exist at the same time.
5.The tendencies of HSP70 protein and mRNA expression are splenogastric hygropyrexia syndrome group＞deficiency of spleen-QI syndrome group＞normal control group,and heavy heat impairing dampness＞simultaneous onset of dampness and heat＞heavy dampness impairing heat.HSP70 expression may be prompted with the certificate type of syndrome may exist a certain degree of correlation.HSP70 was obviously expressed in pyretic syndrome.The proportion of heat or dampness in splenogastric hygropyrexia syndrome can influence the degree of HSP70 expression.
6.HSP70 protein and mRNA expression of Hp-positive group was higher than that of Hp-negative group in splenogastric hygropyrexia syndrome group while HSP70 protein and mRNA expression of Hp-positive group had the higher tendency than that of Hp-negative group in deficiency of spleen-QI syndrome.With gastric mucosal protective effect of HSP70 may represent a certain extent, part of the body antipathogenic qi.Hp infection may increase the mucosa inflammatory,and to cause and increase the mucosal damaged,it may to some part of the representatives of external pathogenic factors.The relationship between HSP70 expression levels and Hp infection may be partly reflected the "antipathogenic qi fighting with pathogenic factors" state of the plenogastric hygropyrexia syndrome.
7.The tendencies of IL-8 protein and mRNA expression are splenogastric hygropyrexia syndrome group＞deficiency of spleen-QI syndrome group＞normal control group,and heavy heat impairing dampness＞simultaneous onset of dampness and heat＞heavy dampness impairing heat.IL-8 is a powerful neutrophil chemotactic factor,and it is related with the inflammatory reaction.IL-8 expression levels may be related to the certain type of syndrome.
8.IL-8 protein and mRNA expression of Hp-positive group had the higher tendency than that of Hp-negative group.IL-8 took an important place in the complex cytokine network,can activate and chemotaxis neutrophils,and played an important role in the inflammatory reaction.It is possibly one of the mechanisms that Hp attack on gastric mucosa in splenogastric hygropyrexia syndrome.
引文
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