Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

Abstract

The Tibetan high plateau is a low-oxygen environment, which may cause the pathogenesis of high-altitude polycythemia (HAPC). Gastric mucosal lesions (GML) are a common complication of HAPC. The molecular mechanisms involved in HAPC-induced GML have remained to be fully elucidated and were therefore investigated in the present study. Gastric tissues of patients with heavy, HAPC-induced GML and healthy controls were assessed by ultrastructural and histopathological analysis. In addition, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect cell apoptosis in the gastric mucosa tissues. Moreover, the expression of genes associated with the phosphoinositide-3 kinase (PI3K) pathway was assessed by RT-qPCR to investigate the mechanism of cell apoptosis in HAPC-induced GML. The results revealed a significant increase in the number of red blood cells, gastric vessels and the diameter of gastric mucosal vessels in HAPC-induced GML patients compared with those in healthy controls. In addition, more red blood cells were distributed in gastric tissue not only at the vascular level but also in the tissue space. The number of vacuoles was increased in the gastric mucosal cells. Furthermore, a significant increase in apoptosis of the gastric mucosal cells was identified. The expression of phosphatase and tensin homolog was significantly higher in gastric mucosa from patients with HAPC-induced GML compared with that in the healthy controls. All of the pathologic changes suggested that significant cell apoptosis occurred in the HAPC-induced GML tissues, which may be associated with the PI3K pathway. These findings may provide novel insight for the treatment of gastric lesions caused by HAPC in the future.

Keywords: PTEN; apoptosis; gastric mucosal lesion; high-altitude polycythemia; mechanism.

Figure 1.

Endoscopic examination of the upper gastrointestinal tract in patients with high-altitude polycythemia-induced gastric mucosal lesions and healthy controls. The upper gastrointestinal tract includes esophagus (P1/N1), cardia (P2/N2), gastric fundus (P3/N3), gastric antrum and body (P4/N4), the duodenal bulb (P5/N5) and descending portion (P6/N6). N, normal healthy subjects; P, polycythemia patients.

Figure 2.

Histopathological changes in gastric mucosa sections. (A) Hematoxylin-eosin staining of gastric mucosa in the antrum region of the HAPC-induced GML group and the control group (magnification, ×400). (B) Number of gastric vascular vessels in the antrum region of the HAPC-induced GML group and the control group. (C) Average diameter of gastric vessels in the antrum region. (D) Number of erythrocytes in the gastric mucosa of each group. Values are expressed as the mean ± standard deviation (n=3). *P<0.05. HAPC, high-altitude polycythemia; GMC, gastric mucosal lesions.

Figure 3.

Cell apoptosis in HAPC-induced GML. (A) Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling analysis was used to compare the amount of apoptotic gastric cells between HAPC-induced GML patients and healthy controls (magnification, ×400). (B) Quantitative analysis of apoptotic molecules in gastric cells assessed by reverse-transcription quantitative polymerase chain reaction analysis. β-actin gene was used as an internal control. Values are expressed as the mean ± standard deviation (n=3). *P<0.05. HAPC, high-altitude polycythemia; GMC, gastric mucosal lesions; Bax, B-cell lymphoma 2-associated X protein.

Figure 4.

Mechanism of GML induced by HAPC. (A) Quantitative analysis of PTEN, PI3K and Akt molecules in gastric cells assessed by reverse-transcription quantitative polymerase chain reaction analysis. β-actin gene was used as an internal control. Values are expressed as the mean ± standard deviation (n=3). *P<0.05. (B) Quantitative analysis of PTEN in gastric cells assessed by western blotting. (C) Quantitative analysis of PTEN in gastric cells assessed by immunohistochemistry (magnification, ×400). HAPC, high-altitude polycythemia; GMC, gastric mucosal lesions; PTEN, phosphatase and tensin homolog; PI3K, phosphoinositide-3 kinase.