Expression And Significance Of TRPV5 In The Kidney Tissue Of Rats With Ceftriaxone Stones

Objective Ceftriaxone as the third-generation cephalosporin is one of commonly used antibiotics in clinical.Because of its small side effect, the advantages of broad spectrum antimicrobial,it is widely used in the treatment of infections in recent years.After the application of ceftriaxone, however, the incidence of renal stones reported in the domestic and foreign literature significantly increased. Yet studies have not found its formation mechanism. Generally speaking, it is believed that ceftriaxone sodium in the body without bioconversion is dissociated of ceftriaxone ion and sodium ion, and combined with calcium in the kidney collecting system, forming difficult soluble precipitation, which leading to the occurrence of kidney stones.TRPV5(Transient receptor potential vanilloid-5)instantaneity receptor potential channel(TRP) is one of members of the family of vanilloid receptor. TRPV5 as an important epithelium of urinary calcium reabsorption channel proteins, regulating the urinary calcium levels,closely associated with urinary calcium excretion, And it is also closely associated with the formation of kidney stones.The aim of the experiment was to build the rat renal ceftriaxone stones model, preliminary to explore the expression of the transient receptor potential vanilloid 5(TRPV5) in kidney tissue of the rats with ceftriaxone stones.To investigate its expression associated with the length of ceftriaxone intervention and provide new theoretical basis for studying the mechanism of ceftriaxone stones.Methods A total of 30 rats were randomly divided into 3 groups, with 10 in each group.Rats in group A were lavaged with 120mg/kg distilled water for 4 weeks, rats in group B were lavaged with 120mg/kg ceftriaxone for 2 weeks and rats in group C were lavaged with 120mg/kg ceftriaxone for 4 weeks.Application of the kit to test rat renal function and the changes of urine biochemical index. Kidney stone formation was observed by using polarization microscope. Immunohistochemistry was used to detect the expression of TRPV5 protein.The double antibodies sandwich ELISA was used to detect the expression of TRPV5 protein.Results The serum calcium has no significant differences among the groups(P>0.05).Compared with group A, the Scr significantly increases in the group C[(96.29±21.81)umol/L vs(34.72±10.49)umol/L,P<0.05].And the Scr increases in the group C,compared with group B[( 96.29 ± 21.81) umol/L vs(59.98 ±20.45)umol/L,P<0.05]; Compared with group A,urine calcium increases in the group C [(0.72±0.25)mmol/L vs(0.46±0.23)mmol/L,P<0.01]; Compared with group A,the Ucr decreases in the C[(2488.28±435.75)umol/L vs(3463.57±221.76)umol/L,P<0.01];By observing group C has large stones crystallization under polarization microscope.Compared with group A and B,the expression of TRPV5 significantly decreases in the group C[(217.79±48.31)ng/L vs(395.66±74.69)ng/L、(343.08±74.08)ng/L,P<0.01];The expression of TRPV5 in serum has no difference among the groups(P>0.05).Conclusions1. Calculus could be observed in the kidney and ureter of rats in group C,demonstrating the model of calculus, ceftriaxone could cause kidney stones.2. Ceftriaxone sodium influences the level of urinary calcium excretion which negatively correlated with the length of ceftriaxone intervention.3. Immunohistochemical and Elisa analysis results showed that the expression of TRPV5 is significantly reduced in the rat renal tissue with application of ceftriaxone 4weeks and negatively correlated with the length of ceftriaxone intervention.Ceftriaxone may suppress expression of TRPV5 in the renal tissue,and increase the renal tubular urinary calcium excretion to promote renal calcium ceftriaxone stones formation.