离体壁细胞研究模型的建立及壁细胞泌酸机制的若干研究
摘要
消化性溃疡是常见的胃肠疾病，壁细胞分泌的胃酸在溃疡病的发生与进展中起着举足轻重的作用，因而对胃酸分泌的研究一直受到高度重视。由于壁细胞功能的调节是神经、体液因素综合作用的结果，在组织、器官水平很难研究单因素对酸分泌的影响，因而建立体外壁细胞研究模型十分必要。目前，国内尚未建立壁细胞分离与研究方法，从而限制了壁细胞的研究进程，也影响了胃肠激素作用机制以及消化性溃疡的病理生理和药理研究。
本研究试图通过以下工作来加强我国在这一领域研究中的某些薄弱环节：
1．建立壁细胞的分离方法并进行离体壁细胞生物活性鉴定：用粗制胶原酶和钙离子螯合剂EDTA消化钝性剥离的胃粘膜，分散的胃粘膜细胞进行细胞淘洗，收集壁细胞并用Percoll密度梯度离心进一步纯化。用台盼兰及HE染色鉴定存活度及纯度；用丫啶橙、~(14)C-氨基比林摄取鉴定壁细胞的酸分泌功能：用RT-PCR检测壁细胞特异的H~+-K~+ ATPase α-亚基基因表达。
2．离体壁细胞泌酸作用调节机制的研究，特别是生长抑素-14(SS-14)和某些抑酸药物对壁细胞作用的机制研究。现已发现生长抑素受体有5种亚型。传统观念认为生长抑素抑酸主要是通过抑制G细胞和ECL细胞的功能间接实现的，但生长抑素对壁细胞酸分泌有无直接抑制作用，是由何种受体亚型介导，以及生长抑素和它的受体亚型特异性激动剂对H~+-K~+ ATPase有无影响，均尚未见文献报道。我们以~(14)C-氨基比林摄取为指标，观察了SS-14及某些生长抑素受体亚型特异性激动剂对组胺诱导的酸分泌的影响；用RT-PCR及原位杂交方法研究了壁细胞生长抑素受体亚型的表达；并应用RT-PCR及Northern杂交方法，观察了SS-14及不同受体亚型激动剂对H~+-K~+ATPase α-亚基基因表达的影响。
Peptic ulcer is a common gastrointestinal disease. Gastric acid secreted by parietal cells plays an important role in the pathogenesis and progressions of ulcer, and has since been paid much more attention to. The regulation of parietal cell function is accomplished by a variety of factors including neuropeptides and neurochemical mediators and it is difficult to study the effect of any single factor on gastric acid secretion at tissue or organ levels. It is therefore necessary to establish an in vitro model of parietal cells. So far the method for isolating parietal cells has not yet been developed in this country, which retards the progression of parietal cell study, including the mechanisms of GI hormones as well as the pathophysiology and pharmacology of peptic ulcer.
The current study was an attempt to upgrade the study in this field in our country.
To establish the method of isolating parietal cells and characterizing its biological activity. Gastric mucosa was stripped bluntly and digested with crude collogenase and EDTA, The dispersed gastric mucosal cells were loaded and pumped into an elutriation chamber. After centrifugation, the cell fractions were collected, and were then subjected to Percoll density-gradient centrifugation for further purification. The viability of cells was defined with trypan blue staining, and parietal cells were identified with HE staining. Accumulation of ~(14)C-aminopyrine in the parietal cells and acridine orange staining were used to assess the acid secretion function. The H~+-K`+ATPase a-subunit gene expression was
本研究试图通过以下工作来加强我国在这一领域研究中的某些薄弱环节：
1．建立壁细胞的分离方法并进行离体壁细胞生物活性鉴定：用粗制胶原酶和钙离子螯合剂EDTA消化钝性剥离的胃粘膜，分散的胃粘膜细胞进行细胞淘洗，收集壁细胞并用Percoll密度梯度离心进一步纯化。用台盼兰及HE染色鉴定存活度及纯度；用丫啶橙、~(14)C-氨基比林摄取鉴定壁细胞的酸分泌功能：用RT-PCR检测壁细胞特异的H~+-K~+ ATPase α-亚基基因表达。
2．离体壁细胞泌酸作用调节机制的研究，特别是生长抑素-14(SS-14)和某些抑酸药物对壁细胞作用的机制研究。现已发现生长抑素受体有5种亚型。传统观念认为生长抑素抑酸主要是通过抑制G细胞和ECL细胞的功能间接实现的，但生长抑素对壁细胞酸分泌有无直接抑制作用，是由何种受体亚型介导，以及生长抑素和它的受体亚型特异性激动剂对H~+-K~+ ATPase有无影响，均尚未见文献报道。我们以~(14)C-氨基比林摄取为指标，观察了SS-14及某些生长抑素受体亚型特异性激动剂对组胺诱导的酸分泌的影响；用RT-PCR及原位杂交方法研究了壁细胞生长抑素受体亚型的表达；并应用RT-PCR及Northern杂交方法，观察了SS-14及不同受体亚型激动剂对H~+-K~+ATPase α-亚基基因表达的影响。
Peptic ulcer is a common gastrointestinal disease. Gastric acid secreted by parietal cells plays an important role in the pathogenesis and progressions of ulcer, and has since been paid much more attention to. The regulation of parietal cell function is accomplished by a variety of factors including neuropeptides and neurochemical mediators and it is difficult to study the effect of any single factor on gastric acid secretion at tissue or organ levels. It is therefore necessary to establish an in vitro model of parietal cells. So far the method for isolating parietal cells has not yet been developed in this country, which retards the progression of parietal cell study, including the mechanisms of GI hormones as well as the pathophysiology and pharmacology of peptic ulcer.
The current study was an attempt to upgrade the study in this field in our country.
To establish the method of isolating parietal cells and characterizing its biological activity. Gastric mucosa was stripped bluntly and digested with crude collogenase and EDTA, The dispersed gastric mucosal cells were loaded and pumped into an elutriation chamber. After centrifugation, the cell fractions were collected, and were then subjected to Percoll density-gradient centrifugation for further purification. The viability of cells was defined with trypan blue staining, and parietal cells were identified with HE staining. Accumulation of ~(14)C-aminopyrine in the parietal cells and acridine orange staining were used to assess the acid secretion function. The H~+-K`+ATPase a-subunit gene expression was
引文
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