Authors

Haiying Zhang*, Kun Han**, Tingfang Chen*, Ruifeng Yang*, Lingling He*, Xinbei Chang*, Zhenzhen Jiang*, Yan Wu*, Fusong Jiang***, #

Departments

*Department of Renal Rheumatism, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, PR China - **Department of Internal Medicine-Oncology, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, PR China - ***Department of Endocrine, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, PR China

Abstract

Objective: We sought to investigate the effect of variations in pH on vascular calcification (VC) in rats with chronic kidney disease (CKD) and the expression of Runt-related transcription factor 2. 

Methods: A total of healthy male Sprague-Dawley rats of a clean grade were randomly stratified into a control group, CKD group, CKD with VC (CKD+VC) group, acid intervention (CKD+VC+AC) group, and alkaline intervention (CKD+VC+AC) group. Rat models with CKD, chronic metabolic acidosis, and chronic metabolic alkalosis were established. Rat arterial pH values and HCO3- concentrations were detected by blood gas analysis. Serum creatinine (SCR) and urea nitrogen (BUN) content were detected by automatic biochemical analysis. Calcium content was determined by o-cresol oxime complex ketone colourimetry. The calcification condition of rat thoracic aorta and Runt-related transcription factor 2 expression were detected by Von Kossa staining and immunohistochemistry, respectively. 

Results: The levels of SCR and BUN were much higher in the CKD group, CKD+VC group, CKD+VC+AC group, and CKD+VC+BC group than in the control group (P<0.05). Separately, pH level and HCO3- concentration results were much lower in the CKD+VC+AC group than in the CKD+VC group (P<0.05) but were much higher in the CKD+VC+BC group than in the CKD+VC group (P<0.05). Also, the calcium contents of the thoracic aorta were significantly higher in the CKD+VC and CKD+VC+BC groups than in the control group, much lower in the CKD+VC+AC group than in the control group, and much higher in the CKD+VC+BC group than in the control group. (P<0.05). There were many brown-black calcium deposits noted in the media layer of the thoracic aorta of rats in the CKD+VC group and CKD+VC+BC group (P<0.05), while no such findings were observed in the control group, CKD group, or CKD+VC+AC group (P<0.05); further, the level of brown-black calcium deposition in the media layer of the thoracic aorta was much higher in the CKD+VC+BC group than in the CKD+VC group (P<0.05). Finally, the CKD+VC group and CKD+VC+BC group had significantly higher RUNX2 immunohistochemical scores than did the control group or CKD group (P<0.05), while the RUNX2 immunohistochemical scores were much lower in the CKD+VC+BC but much higher in the CKD+VC+BC group than in the CKD+VC group (P<0.05).

Conclusions: An acidic pH environment inhibits the occurrence of VC in rats with CHD and an alkaline environment promotes VC in rats with the same, which may be achieved by regulating RUNX2 expression.

Keywords

PH, rats with chronic kidney disease, vascular calcification, Runt-related transcription factor 2.

DOI:

10.19193/0393-6384_2020_3_226