2022, Vol. 26 ›› Issue (29): 4616-4623

Protective effects of tertiary butylhydroquinone on various organs in type 2 diabetic rats

Tian Min, Liu Yuting, Xie Like, Cao Yang, Lyu Hongbin   

Abstract: BACKGROUND: Diabetes can cause dysfunction of the whole body tissues and organs. 6-Phosphofructokinase-2/fructose bisphosphatase-2 isoenzyme 3 (PFKFB3) and sphingosine 1-phosphate receptor 2 (S1P2) may be related to the complications of diabetes. Tertiary butylhydroquinone has a certain protective effect on the complications of diabetes.
OBJECTIVE: To study the expression of PFKFB3 and S1P2 in various organs (heart, retina, kidney, and aorta) of type 2 diabetic rats and to explore the relationship between tertiary butylhydroquinone and PFKFB3 and S1P2.
METHODS: Twenty-four male Sprague-Dawley rats were divided into normal control group, diabetic group and tertiary butylhydroquinone group. Diabetic models were made in the latter two groups. At 7 days after modeling, the rats in the tertiary butylhydroquinone group were fed with high-fat and high-sugar diet containing 1% tertiary butylhydroquinone, while those in the diabetic group continued to be fed with high-fat and high-sugar diet. After 12 weeks of intervention, the blood glucose and insulin levels were detected; immunohistochemistry and qRT-PCR were used to detect the distribution and expression of PFKFB3 and S1P2 at protein and mRNA levels, respectively; and TUNEL method was used to detect the apoptosis index in different rat organ cells.
RESULTS AND CONCLUSION: There was an overall significant difference in the blood glucose and insulin levels between groups (P=0.000, P=0.000). PFKFB3 and S1P2 were mainly distributed in the retinal ganglion cell layer, the inner nuclear layer, aortic intima endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells. The relative protein and mRNA levels of PFKFB3 and S1P2 were significantly different in the retina, aortic intimal endothelial cells, cardiomyocytes, interstitial myocardial endothelial cells, and renal tubular cells (all P < 0.05). The overall difference in the relative expression of S1P2 protein and mRNA in the glomerulus was statistically significant (all P < 0.05). Compared with the normal control group, the expression of PFKFB3 and S1P2 was significantly increased in the diabetic group (P < 0.05), while compared with the diabetic group, the expression of PFKFB3 and S1P2 was significantly decreased in the tertiary butylhydroquinone group (P < 0.05). TUNEL results indicated that there was an overall significant difference in the apoptotic index of rat retinal ganglion cells, cardiomyocytes, renal tubular cells, and aortic full-thickness cells between groups (all P < 0.05). The overall apoptotic index of various organs in the diabetic group was significantly higher than that in the normal control group (P < 0.05), while compared with the diabetic group, the overall apoptotic index was significantly reduced in the tertiary butylhydroquinone group (P < 0.05). To conclude, PFKFB3 and S1P2 are the metabolites involved in the pathological process of various organs in diabetic rats and may be related to the apoptosis of cells in various organs of diabetic rats. Tertiary butylhydroquinone can reduce the expression of PFKFB3 and S1P2 and reduce cell apoptosis in various organs, indicating that tertiary butylhydroquinone has a certain protective effect on various organs of type 2 diabetic rats.
Key words: PFKFB3, S1P2, tertiary butylhydroquinone, diabetes, heart, retina, kidney, aorta