The Effect of Prolactin on Chronic Kidney Disease

• Main Authors: Hsiao-Hsin Lin, 林孝欣
• Other Authors: William J. Huang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/61866224586053632059

碩士 === 國立陽明大學 === 生理學研究所 === 102 === Chronic kidney disease is a common worldwide problem. About 30% of the patients with chronic kidney disease demonstrate hyperprolactinemia (hyperPRL). In the late stage of the disease, more than 70% of patients develop hyperPRL. Prolactin (PRL) is a peptide hormone primarily produced by the lactotroph in the anterior pituitary, and is well known for its physiological function in lactation. The aim of our study is to examine the role of PRL in chronic kidney disease. First, we used AP-grafted model to induce hyperPRL in rats. Function of kidney was evaluated by spot urine protein excretion calibrated by urine creatinine. At sacrifice, kidney section was processed for immunohistochemistry staining and kidney protein extracted for western blot analysis. Expression of nephrin, WT-1 and other cytokines were assessed. The results showed that there was no significant difference between CX-grafted and AP-grafted rats. Secondly, we combined AP-grafted hyperPRL model and unilateral ureteral obstruction (UUO) model to observe the effect of hyperPRL on impaired kidney function. Unilateral ureteral obstruction was made after 6 weeks of AP transplantation. The rats were sacrificed 2 weeks later. Then, the renal tissue was collected for western blot for the expression of nephrin and WT-1. PAS stained sections were used to analyze renal histology features. There was no significant difference in nephrin and WT-1 expression. In UUO+AP group, glomerulosclerosis and tubulointerstitium scores were significantly increased. Thirdly, we used 5/6 nephrectomy (5/6 NX) to examine the effect of PRL. Two months after 5/6 NX surgery, ovine prolactin (o-PRL, 50IU/kg/day) was daily administrated subcutaneously for 7 days. During the treatment period, the rats were transferred to metabolic cages for urine and faeces collection. Urine creatinine, urine protein, blood creatinine and blood urine nitrogen (BUN) were measured as indicators of renal functions. At sacrifice, the remaining kidney tissue was retrieved for further evaluation. Periodic acid-Schiff (PAS) stained sections were analyzed for the renal histology features. In 5/6 NX group, water consumption, urine output, urine creatinine, urine protein, blood creatinine and BUN increased more significantly than that of the control group. Besides, adhesion formation between the glomerular tufts and the Bowman’s capsules and mesangial matrix expansion were observed in 5/6 NX group. Our results showed that 5/6 NX did increase glomerulosclerosis and tubulointerstitial inflammation. After o-PRL treatment, the kidney demonstrated a more significantly increased in proportion of glomerulosclerosis and tubulointerstitium inflammation. The findings suggest that PRL might have detrimental effects on glomeruli and tubulointerstitium. In conclusion, hyperPRL has little effects (although with a protective trend) on kidney at normal renal function. However, in chronic kidney disease, PRL seems to have detrimental effects on kidney function.