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Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway.

Abstract

Aim

Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats.

Methods

Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry.

Results

Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment.

Conclusion

WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway.

Authors+Show Affiliations

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31320912

Citation

Yin, Jing, et al. "Weiqi Decoction Attenuated Chronic Atrophic Gastritis With Precancerous Lesion Through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway." Evidence-based Complementary and Alternative Medicine : ECAM, vol. 2019, 2019, p. 2651037.
Yin J, Yi J, Yang C, et al. Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway. Evid Based Complement Alternat Med. 2019;2019:2651037.
Yin, J., Yi, J., Yang, C., Xu, B., Lin, J., Hu, H., ... Fei, X. (2019). Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway. Evidence-based Complementary and Alternative Medicine : ECAM, 2019, p. 2651037. doi:10.1155/2019/2651037.
Yin J, et al. Weiqi Decoction Attenuated Chronic Atrophic Gastritis With Precancerous Lesion Through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway. Evid Based Complement Alternat Med. 2019;2019:2651037. PubMed PMID: 31320912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway. AU - Yin,Jing, AU - Yi,Jinyu, AU - Yang,Chun, AU - Xu,Bo, AU - Lin,Jiang, AU - Hu,Hongyi, AU - Wu,Xiaojun, AU - Shi,Hailian, AU - Fei,Xiaoyan, Y1 - 2019/06/20/ PY - 2019/04/30/received PY - 2019/06/04/accepted PY - 2019/7/20/entrez PY - 2019/7/20/pubmed PY - 2019/7/20/medline SP - 2651037 EP - 2651037 JF - Evidence-based complementary and alternative medicine : eCAM JO - Evid Based Complement Alternat Med VL - 2019 N2 - Aim: Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats. Methods: Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry. Results: Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment. Conclusion: WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway. SN - 1741-427X UR - https://www.unboundmedicine.com/medline/citation/31320912/Weiqi_Decoction_Attenuated_Chronic_Atrophic_Gastritis_with_Precancerous_Lesion_through_Regulating_Microcirculation_Disturbance_and_HIF-1α_Signaling_Pathway L2 - https://dx.doi.org/10.1155/2019/2651037 DB - PRIME DP - Unbound Medicine ER -