Study Of Relativity Between Apelin-APJ Level And Hypertensive Kidney Damage

Objective:To discuss the correlation between Apelin-APJ level and early renal damage caused by hypertension, and to evaluate whether it can be regarded as an early diagnosis index of kidney damages.Methods:1. Clinical research:eighty-eight essential hypertension (EH) patients were selected. By method of enzyme linked immunosorbent assay (ELISA), the serum Apelin was assessed., Urinary microalbumin (mALB), blood and urine (32-microglobulin β2-MG) were detected by latex enhancement immunoturbidimetry. Urease ultraviolet rate method was used to detect urea nitrogen (BUN) and enzymatic-measured blood creatinine (CR). Cockcroft formula was utilized to calculate endogenous creatinine clearance (CCr). The urine N-acetyl-P amino glycosidase (NAG) and24-hour urinary albumin (24HUTP) were detected by end point method. Statistical analysis of all patients’serum apelin level and the renal function indexes were performed. Regarding the blood β2-MG value (0.8-3mg/1) as the standard, eighty-eight EH patients were divided into two groups:blood β2-MG lower than3mg/1for normal renal group (group A) and blood β2-MG higher than3mg/1for renal damage group (group B). Statistics analysis was applied to compare the differences of serum apelin level and the other renal function indices between the two groups.2. Animal research:the research objectives are12weeks male Wistar rats (WKY12)8,12weeks male spontaneously hypertensive rats (SHR12)8and16weeks male spontaneously hypertensive rats (SHR16)8. Noninvasive tail arterial blood pressure measurement system was used to determine the rats systolic blood pressure. The serum Apelin and angiotensin II(Ang II) levels were analyzed by means of enzyme linked immunosorbent assay(ELISA). Urease ultraviolet rate method and enzymatic method were used to detect blood BUN, CR and β2-MG. At the same time, taking kidneys of all rats. The HE dyeing method was used to observe the glomerular form. The RT-PCR method was applied to detect Apelin and APJ mRNA expression levels in kidney. To analyze the varying pattern of renal Apelin-APJ system during the development of hypertension, and the relationship between the system and renal function.Results:1. Clinical studies:For EH patients. there were significant negative correlations between serum Apelin and serum β2-MG, urine β2-MG (P<0.05), and there no correlations between serum Apelin and other renal function indices (P>0.05). Compared with group A, serum apelin and Ccr levels reduced significantly (P<0.05);(32-MG, BUN and Cr increased (P<0.05); NAG and PRO in urin rised (P<0.05); urinal MAL and β2-MG increased (P<0.01) in group B.2. Animal studies:For rats in WKY12group, SHR12group and SHR16group, blood pressure and KW/BW ratio increased gradually. The differences were statistically significant (P<0.01). Serum apelin level in SHR12group was significantly reduced (4.31±0.34ng/ml vs4.91±0.44ng/ml, P<0.05), and reduced further in SHR16group (3.38±0.58ng/ml vs4.31±0.34ng/ml, P<0.01). The β2-MG, BUN, Cr, Ang Ⅱ levels in SHR12group presented rising trend, however, the differences were not statistically significant (P>0.05) until to SHR16group (P<0.01). RT-PCR detection results showed that for three groups of rats, renal apelin-mRNA expression levels were gradually reduced (P<0.01):SHR12group vs WKY12group(0.306±0.017vs0.597±0.022,P<0.01), SHR16group vs SHR12group (0.171±0.038vs0.306±0.017, P<0.01). The expression of APJ-mRNA showed the same trends as Apelin-mRNA:SHR12group vs WKY12group (0.316±0.028vs0.620±0.008, P<0.01), SHR16group vs SHR12group (0.170±0.039vs0.316±0.028, P<0.01). The observation by light microscopy showed that there was no pathological changes for the WKY12group kidney. The wall of renal glomerulus and leaf arterial were thickened at SHR12group and SHR16rats, and Glomerulus were atrophic with partly decompensated hypertrophy, passive congestion and thickened basement membrane. The above pathological changes were more serious at SHR16group than SHR12group.Conclusions:1. Serum Apelin levels and hypertensive early kidney damage markers of blood and urine β2-MG levels were significantly negatively correlated and may be used as one of the detection indexes reflecting hypertensive renal damage.2. Apelin-APJ levels of early markers of kidney damage appeared earlier than traditional hypertension and it might become one of the early diagnostic indexes of hypertensive renal damage.