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Background@#Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN. @*Methods@#Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups. @*Results@#The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5´-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression. @*Conclusion@#Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.
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Objective To investigate the effects of 12-lipoxygenase (12-LO) and angiotensin Ⅱ (Ang Ⅱ) on the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) p21,p27 and p57 related to cell hypertrophy.Methods Mesangial cells were treated with high glucose for 24 hours and 48 hours respectively.12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and Ang Ⅱ were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed high fat diet were received low dose streptozotocin (STZ) to make type 2 diabetes (DN).The rats were divided into normal control group,DN group,DN+Ang Ⅱ type 1 receptor blocker (ARB) group or 12-LO inhibitor (CDC) group.DN+ARB rats were treated by losartan for 6 weeks,and DN+CDC rats were treated for 8 weeks.Urine albumin and protein expressions of p21,p27 and p57 were detected by ELISA and Western blotting respectively.Glomeruli injury and expressions of p21 and p27 were detected by PAS staining and immunohistochemistry respectively.Results High glucose increased p21 and p27 protein expression in mesangial cells significantly compared with the relative control (all P ＜ 0.05),but had no effect on p57.Ang Ⅱ increased p27 protein expression in gloneruli significantly (P ＜ 0.05),but had no effect on p21 and p57 protein expression.12(S)-HETE increased both p21 and p27 protein expression in glomeruli significantly (all P ＜ 0.05),but had no effect on p57 protein expression.Blood glucose,kidney/body weight,urinary protein,and glomerular p21 and p27 protein expressions were increased in DN group (all P ＜ 0.05) compared with those in control group,with little change of p57 protein expression (P ＜ 0.05).Moreover,glomerular hypertrophy and extra cellular matrix accumulation were observed in DN group.However,urine protein,kidney/body weight,renal injury,but not blood glucose,were decreased in DN+ARB group and DN+CDC group compared with DN group respectively (P＜ 0.05).Further DN+CDC rats had decreased both p21 and p27 protein expressions in glomeruli,but DN+ ARB rats only had decreased p27 protein expression (all P ＜ 0.05).Conclusions 12-LO may induce both p21 and p27 protein expression in DN glomeruli,but Ang Ⅱ may induce only p27 expression.
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Objective To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease (ESRD).Methods Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials,EMBASE,CNKI,Wanfang database.Data extracted from the literatures were analyzed with the Cochrane Collaboration's RevMan 5.1 software.Results Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR =1.00,95 ％ CI (0.92-1.09),P =0.97],and more effective than placebo [RR=4.69,95％ CI (2.63-8.39),P＜ 0.01] (intervention dose≤ 1500 mg) and [RR =18.92,95％ CI (7.42-48.22),P ＜ 0.01] (intervention dose ＞ 1500 mg).In comparison with calcium carbonate group,the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR =0.06,95 ％ CI (0.01-0.72),P =0.03],while the incidence of nausea [RR =1.80,95 ％ CI(0.70-4.64),P =0.22],vomiting [RR =3.94,95％ CI (0.45-34.38),P=0.22] and constipation [RR=0.82,95％ CI (0.49-1.37),P=0.45] were similar.The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo,with lower incidence of constipation [RR =0.19,95 ％ CI (0.06-0.59),P ＜ 0.01].Conclusions The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate.The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate,and the incidence of gastrointestinal adverse effect such as nausea,vomiting and constipation are similar with calcium carbonate.
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Objective To investigate the effect of angiotensin Ⅱ (Ang Ⅱ) type 1 receptor blocker (ARB) on 12-lipoxygenase (12-LO) activity and P-cadherin expression in type 2 diabetic rat glomeruli.Methods Podocytes were stimulated by 107 mol/L Ang Ⅱ for 24 hours.12(S)-HETE (1mg· kg 1 · d-1) and Ang Ⅱ (400 ng· kg-1· min-1) were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed with high fat diet received low dose streptozotocin (STZ) to make type 2 diabetes and divided into 2 groups:low dose STZ (DN group),low dose STZ + ARB treatment (Losartan group).Rats fed with regular chow were used as control group.All the rats were sacrificed after 6 weeks.Urine,blood,kidney cortical tissue and isolated glomeruli by sieving method were collected at the end of study respectively.ELISA,RT-PCR and Western blotting for related target were performed respectively.Results Ang Ⅱ increased 12(S)-HETE levels in podocytes and glomeruli (all P ＜ 0.01).Ang Ⅱ levels in the glomeruli were significantly increased by 12(S)-HETE stimulation (P ＜0.01).Blood glucose,kidney/body weight and 24 hour urinary protein were increased in DN group compared with that in control group (all P ＜ 0.01).However,urine protein,Kidney/body weight were decreased in Losartan group compared with DN group (all P ＜ 0.05).Increment of 12(S)-HETE content and decrement of P-cadherin expression were observed in DN glomeruli compared with that in control group(all P ＜ 0.01).These abnormalities were prevented by administration of the losartan (all P ＜ 0.05).Conclusions Ang Ⅱ can down-regulate glomerular P-cadherin expression via activation of 12-LO.ARB can ameliorate the progression of DN via up-regulation of glomerular P-cadherin through inhibition of 12-LO activation in type 2 DN rats.