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Effect Of 1, 25- Dihydroxy Vitamin D3 On IL-23/IL-17 Axis In Rats With IgA Nephropathy

Posted on:2017-05-28Degree:MasterType:Thesis
Country:ChinaCandidate:L PengFull Text:PDF
GTID:2284330503963473Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Objective:To observe the expression of IL-23 and IL-17, and to discuss the effects of 1, 25(OH)2D3 on IL-23/IL-17 axis in rats with experimental Ig A nephropathy. Methods:We choosed 52 wistar rats,with which 42 rats were established Ig A nephropathy model by using bovine gamma globulin to stimulate the mucosal immune system directly, while other 10 rats were choosed in control group(group A) in random, The control group was given the equivalent distilled water via intragastric infusion and physiological saline tail intravenous injection.Excluding the death rats after we use the the method of pathology to test the success of building the experimental Ig A nephropathy model, the successful rats models were randomly divided into model group(group B), 1,25(OH)2D3 therapy group(Group C), prednisone therapy group(Group D), and prednisone+1,25(OH)2D3 combination therapy group(Group E), 8 rats in each group.Rats in B group were given intragastric infusion of 1,25(OH)2D3 in 3ng/100 g everday; rats in C group were given intragastric infusion of prednisonein in 10mg/kg everday; in E group,rats were given the same aboved-mentioned amount of prednisonein and calcitriol everday;in the A group and B group, the same amount of distilled wateron was given everday..After two weeks treatment, the change of red blood cells in urine, 24 hour proteinuria, serum creatinine, serum calcium and phosphorus of rats were detected and the IL-23 m RNA and IL-17 m RNA levels in spleen by using RT-PCR were detected.At the same time, the changes of IL-17 and IL-23 in the kidneys were detected by using Immunohistochemistry Results:(1)24 hour proteinuria(mg/24h): Group A(normal control group) was 7.01±0.23, group B(model group) was 51.16±2.12, group C(1, 25(OH)2D3 treatment group) 26.15±1.97, group D(prednisone treatment group) was was12.99±1.52, E group(prednisone +1, 25(0H) 2D3 combined treatment therapy group) was9.89±1.60. The 24 h urine protein of B group was significant higher than A group(p<0.05). After treatment, the 24 h proteinuria of each group was declined significantly compared with the B group(p<0.05).(2)Urine red blood cell count(/ul): A group was 2.3±1.4; B group was 375±16.68, C group was 157±20.7, D group was 20±3.37, E group was7±2.96. The urinary red blood cell of B group was significant higher than A group(p<0.05). After treatment, the urinary red blood cell count of each group was declined significantly compared with the B group, the E group decreased most significantly(p<0.05).(3) Level of blood creatinine of rats(μ mol/L) in each group: group A was 45.08±1.82; group B was 44.56±1.16, group C was 44.18±2.0, group D was 43.57±1.50, group E was 43.39±1.65. Level of serum calcium of rats(mmol/L) in each group: group A was 2.22±0.13, group B was2.36±0.19, group C was 2.36±0.15, group D was 2.33±0.19, group E was 2.29±0.12. The serum phosphorus level(mmol/L): A group was 2.81±0.09, B group was 2.83±0.19, C group was 2.71±0.12, D group was 2.72±0.11, E group was 2.80±0.15. Serum creatinine, serum calcium and phosphorus levels showed no statistically significant change(p>0.05).(4) the mean density of IL-23: group A was 0.038±0.009; group B was 0.377±0.021, group C was 0.264±0.011, group D was 0.162±0.009, group E was 0.101±0.016., the mean density of C,D,E groups were significant decreased than B group(p<0.05), and the E group was most significant decreased(p<0.05). the mean density of IL-17: group A was 0.027±0.011; group B was 0.322±0.016, group C was 0.265±0.015, group D was 0.137±0.012, group E was 0.089±0.015., the mean density of C,D,E groups were significant decreased than B group(p<0.05), and the E group was most significant decreased(p<0.05). The expression of IL-23 was positively correlated with the expression of IL-17 in the each group.The expression of IL-23 and IL-17 were positively correlated with the urine protein of 24 hours and the urine red blood cell count of group B(p<0.05), and were no significant correlation with the urine red blood cell count of other groups.(5) The relative contents of IL-23 m RNA and IL-17 m RNA levels in A group were respectively 0.311±0.023 and 0.142±0.005; in B group, they were 0.936±0.020 and 0.846±0.016; in C group, they were 0.760±0.021 and 0.596±0.021;in D group, they were 0.514±0.010 and 0.451±0.021;in E group,they were 0.407±0.020 and 0.311±0.020. The relative contents of IL-23 m RNA and IL-17 m RNA levels in B groups were significant higher than Agroup(p<0.05).After treatment the relative contents of IL-23 m RNA and IL-17 m RNA levels of each group were declined significantly(p<0.05). IL-23 m RNA was positively correlated with the IL-17 m RNA.The IL-23 m RNA and IL-17 IL-17 m RNA were positively correlated with the urine protein of 24 hours and the urine red blood cell count of group B(p<0.05), and were no significant correlation with the urine red blood cell count of other groups.Conclusions:1) IL-23 and IL-17 may participate in the occurrence and development of Ig A nephropathy;2) 1, 25(OH) 2D3 may play a role in immune regulation by downgrading the expression of IL-23/IL-217 axis irectly or indirectly.
Keywords/Search Tags:1,25-dihydroxyvitamin D3, Ig A nephropathy, IL-23/IL-17 axis
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