| ObjectiveObesity is a global existing serious public health problem. Recently, the incidence of obesity is greatly increasing. The prediction shows that there will be fifty eight percent persons who are overweight or obese in the world in 2030. The overweight and obesity increase the risk of the occurrence of type 2 diabetes, mellitus, hypertension, cardiovascular diseases and renal diseases. As early as 1974,it had been known that obesity could lead to proteinuria and it was named obesity-associated glomerulopathy(ORG).After being intervened under peroxisome proliferator activated receptor gamma(PPARγ) agonist pioglitazone, the level of serum adiponcetin(ADP) increased and the urinary microalbumin(m ALB) excretion decreased. The structure of telmisartan is similar to pioglitazone. Telmisartan is a PPARγ agonist too. This study aimed at the influence of telmisartan as a PPARγ agonist effect on serum ADP, urine m ALB excretion, the expression of renal PPARγm RNA and the level of zonula occludens-1(ZO-1) and the changes of the renal pathology of simple obesity mice,and discussed the significance to the treatment of telmisartan as PPARγ agonist for Obesity-related glomerulopathy.Method A total of 24 8-week-old male ob/ob mice and 8 8-week-old male C57 mice were selected for this study. The genetic background of ob/ob mouse was C57 mouse, but the lepin gene was deleted in ob/ob mouse. ob/ob mice were randomly divided in to 3 groups by body weight and fed with high-fat diet for 12 weeks: obesity group(M group), telmisartan intervention group(T1 group) and losartan intervention group(T2 group). C57 mice acted as control group(C group)and were fed with general diet for 12 weeks. Serum ADP and blood glucose were measured before and after treatment. 24 h urine was collected to measure urine m Alb. Quantitative real-time polymerase chain reaction(q RT-PCR) was used to measure the expression level of peroxisome proliferators-activated receptors gamma m RNA(PPARγ m RNA). HE stain was used to observe the morphological changes of kidney and measure the glomerular diameter. The expression level of kidney ZO-1 was measured with immunohistochemical method. Body weight, serum adiponectin level,, urine m Alb level, expression level of kidney PPARγ m RNA, kidney wet weight,glomerular diameter and the expression level of kidney zonula occludens-1(ZO-1)of 4 groups were compared and a correlation analysis was carried out by Person correlation coefficient. The SPSS 20.0 software was used to process and analysis data. P<0.05 was considered to have statistical significance.Results 1.The general condition of mice :1.1 The body weight and urine micro-albumin of ob/ob mice had been in comparison with C57BL/6J mice before the test :The mean body weight of 8-week-old ob/ob mice was significantly higher than C57BL/6J mice(P<0.01).Moreover, the body weight of ob/ob mice was significantly more than 20% of C57BL/6J,which reached the obese standard.the urine micro albumin of ob/ob mice was significantly higher than C57BL/6J mice(P<0.01).The level of serum glucose of all the mice didn’t meet the standards of diabetes although the difference of glucose was significantly between two kinds of mice, then we can make sure that the apparent m ALB of ob/ob mice was caused by obese but not diabetes.1.2 The body weight of every group mice before and after the test: the body weight of M,T1 and T2 group was more than C group before the test(P<0.01);T1 group lower than M and T2 group(P<0.01).There was no difference in the body weight of M and T2 group(P>0.05).2. Urine micro-albumin of 24 mice:2.1 The comparison among four groups:The level of 24 h urine m ALB of M group was higher than before(P<0.01);The level of 24 h urine m ALB of T1 and T2 group less than before(P<0.01); The level of 24 h urine m ALB of C group unchanged(P >0.05).2.2 The comparison among four groups :The level of 24 h urine mALB of M,T1 and T2 group was significantly higher than C group before and after the test(P <0.01); The level of urine m ALB of T1 and T2 group lower than M group(P <0.01,P =0.01).And the level of urine m ALB of T1 group lower than T2 group after the test(P =0.027).3. The serum adiponectin3.1 The comparison among four groups before and after the test:The level of serum adiponectin of M and T2 group after the test was significantly lower than before(P <0.01); The level of serum adiponectin of T2 group higher(P <0.01); The level of serum adiponectin of C group unchanged(P >0.05).3.2 The comparison among four groups :The level of serum adiponectin of M,T1 and T2 group was significantly lower than C group before and after the test(P <0.01); The level of serum adiponectin of M,T1 and T2 group was not significantly different before the test(P =0.174,P =0.183,P =0.973); The level of serum adiponectin of T1 group higher than M and T2 group after the test(P =0.003,P =0.005).There was no statistical significant difference between the level of serum adiponcetin of M and T2 group after the test(P =0.862).4.The expression level of kidney PPARγm RNA: The expression level of kidney PPARγm RNA of C group was higher than M,T1 and T2 group(P <0.01).The expression level of kidney PPARγm RNA of T1 group was higher than M group(P =0.026),The expression level of kidney PPARγm RNA of T1 group higher than T2 group(P =0.035)and there was no statistical significant difference between T2 and M group(P =0.886).5.Changes of kidney pathology:5.1 The renal wet weight(right kidney):The kidney wet weight of C group was less than M and T2 group(P <0.01); The kidney wet weight of M group higher than T1(P =0.005)and no significant difference with T2 group(P =0.377). The kidney wet weight of T1 group lower than T2 group(P =0.04).5.2 Changes of kidney tissue pathology: The glomerulus,Kidney tubule,endothelial cell and glomerular mesangial cells of C and T1 group were normal. The changes include Bowman’s capsule widened,glomerular basement membrane thickening, mesangial cells and mesangial matrix proliferation,glomerular volume increased, some accompanied by focal segmental glomerulosclerosis, tubular atrophy and mild interstitial fibrosis could be found in M and T2 group.5.3 Diameter of glomerular:The diameter of glomerular of M and T2 group was bigger than C and T1 group(P <0.01). The diameter of glomerular of T2 group was bigger than T1 group(P <0.01) and not significant different with M group(P =0.945).6. The expression level of ZO-1 of kidney tissue: ZO-1 was mainly expressed in the cytoplasm. The expression level of ZO-1 of kidney tissue in M and T2 group was lower than C group(P <0.01); The expression level of ZO-1 of kidney tissue of T1 group lower than C group(P =0.079); The expression level of ZO-1 of renal tissue of M and T2 group lower than T1 group(P <0.01).7.Correlation analysis:7.1There was positive correlation of 24 h urine micro-albumin with body weight,right renal wet weight and the diameter of glomerular(r1=0.853,r2=0.631,r3=0.830;P 1<0.01,P2<0.01,P3<0.01)and a negative correlation with the serum ADP,the expression level of kidney PPARγm RNA and the expression level of kidney ZO-1(r4=-0.773,r5=-0.469,r6=-0.731;P4<0.01,P5=0.007,P6<0.01).7.2There was positive correlation of the serum ADP with the expression level of kidney PPARγm RNA and the expression level of kidney ZO-1(r7=0.434,r8=0.811;P7=0.013,P8<0.01)and a negative correlation with body weight,right renal wet weight, urine micro-albumin and diameter of glomerular(r9=-0.743,r10=-0.523,r4=-0.773,r11=-0.722;P9<0.01,P10=0.002,P4<0.01,P11<0.01).7.3 There was positive correlation of kidney PPARγm RNA with the expression level of the serum ADP and ZO-1(r7=0.434,r12=0.386;P7=0.013,P12=0.029)and negative correlation with the body weight,right renal wet weight, urine micro-albumin and diameter of glomeruli(r13=-0.381,r14=-0.340,r5=-0.469,r15=-0.547;P13=0.034,P14=0.04 7,P5=0.007,P15=0.001).7.4 There was positive correlation of the expression level of kidney ZO-1 with the serum ADP,the expression level of kidney PPARγm RNA(r8=0.811,r12=0.386;P8<0.01,P12=0.029)and a negative correlation with body weight,right renal wet weight, urine micro-albumin and diameter of glomeruli(r16=-0.770,r17=-0.493,r6=-0.731,r18=-0.787;P16<0.01,P17=0.004,P6<0.01,P18<0.01).Conclusion 1.The level of serum ADP of obese mice decreased,the urine m ALB of them increased.Renal pathology showed glomerular hypertrophy, in part associated with focal segmental glomerulosclerosis,the expression of ZO-1 in podocyte reduced.2.The ARB can decreased the urine m ALB excretion in obese mice by improving renal hemodynamics and non-hemodynamics.3.Telmisartan compared with losartan had a stronger reducing urine micro-albumin of obesity mice, which may be correlation with the effect of telmisartan acting the PPARγ and promote the level of serum ADP and the expression of ZO-1 in podocyte and inhibit the glomerular hypertrophy. |
PDF Full Text Request