Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Geroscience. 2022 Dec;44(6):2845-2861. doi: 10.1007/s11357-022-00610-7. Epub 2022 Jun 29.
Diabetes, hypertension, and aging are major contributors to cardiovascular and chronic kidney disease (CKD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors have become a preferred treatment for type II diabetic patients since they have cardiorenal protective effects. However, most elderly diabetic patients also have hypertension, and the effects of SGLT2 inhibitors have not been studied in hypertensive diabetic patients or animal models. The present study examined if controlling hyperglycemia with empagliflozin, or given in combination with lisinopril, slows the progression of renal injury in hypertensive diabetic rats. Studies were performed using hypertensive streptozotocin-induced type 1 diabetic Dahl salt-sensitive (STZ-SS) rats and in deoxycorticosterone-salt hypertensive type 2 diabetic nephropathy (T2DN) rats. Administration of empagliflozin alone or in combination with lisinopril reduced blood glucose, proteinuria, glomerular injury, and renal fibrosis in STZ-SS rats without altering renal blood flow (RBF) or glomerular filtration rate (GFR). Blood pressure and renal hypertrophy were also reduced in rats treated with empagliflozin and lisinopril. Administration of empagliflozin alone or in combination with lisinopril lowered blood glucose, glomerulosclerosis, and renal fibrosis but had no effect on blood pressure, kidney weight, or proteinuria in hypertensive T2DN rats. RBF was not altered in any of the treatment groups, and GFR was elevated in empagliflozin-treated hypertensive T2DN rats. These results indicate that empagliflozin is highly effective in controlling blood glucose levels and slows the progression of renal injury in both hypertensive type 1 and type 2 diabetic rats, especially when given in combination with lisinopril to lower blood pressure.
糖尿病、高血压和衰老是心血管疾病和慢性肾脏病（CKD）的主要病因。钠/葡萄糖共转运蛋白 2（SGLT2）抑制剂因其具有心脏和肾脏保护作用，已成为 2 型糖尿病患者的首选治疗药物。然而，大多数老年糖尿病患者也患有高血压，SGLT2 抑制剂在高血压糖尿病患者或动物模型中的效果尚未得到研究。本研究旨在探讨用恩格列净控制高血糖，或与赖诺普利联合使用，是否能减缓高血压糖尿病大鼠肾脏损伤的进展。该研究使用高血压链脲佐菌素诱导的 1 型糖尿病 Dahl 盐敏感（STZ-SS）大鼠和去氧皮质酮-盐诱导的 2 型糖尿病肾病（T2DN）大鼠进行。单独使用恩格列净或与赖诺普利联合使用可降低 STZ-SS 大鼠的血糖、蛋白尿、肾小球损伤和肾纤维化，而不改变肾血流量（RBF）或肾小球滤过率（GFR）。恩格列净和赖诺普利联合治疗还降低了大鼠的血压和肾脏肥大。单独使用恩格列净或与赖诺普利联合使用可降低血糖、肾小球硬化和肾纤维化，但对高血压 T2DN 大鼠的血压、肾脏重量或蛋白尿无影响。在任何治疗组中，RBF 均未改变，而恩格列净治疗的高血压 T2DN 大鼠的 GFR 升高。这些结果表明，恩格列净在控制血糖水平和减缓高血压 1 型和 2 型糖尿病大鼠肾脏损伤进展方面非常有效，尤其是与赖诺普利联合使用以降低血压时。
