ABSTRACT
Objective The study is to investigate the role of miR-328 in endothelial mesenchymal transition (EMT)induced by high glucose in human umbilical vein endothelial cells (HUVECs)and its signaling mechanism.Methods HUVECs were cultured in high glucose environment to induce EMT;The recombinant lentiviruses were created by miR-328 and antagomiR- 328 transfection of HUVECs.The experiment was divided into seven groups: normal glucose;mannitol group;high glucose;miR-328;miR-328 virus negative control;high glucose + U0126;miR-328 + U0126.Double immunofluorescent staining was used to determine expression of EMT markers;Changes in miR-328 expression is examined by RT-qPCR;The expressions of type Ⅰ/Ⅲ collagen,p-MEK1/2 and p-ERK1/2 are examined by Western blot.Results 1)HUVECs showed positive staining for CD31 and α-SMA in high glucose group.2)The expression of miR-328 was up-regulated(P<0.05)in HUVECs treated by high glucose or miR-328.Compared with high glucose group or miR-328 group,miR-328 expression was less pronounced aftertreatment with U0126.3)The expressions of type Ⅰ/Ⅲ collagen increased in HUVECs treated by high glucose or miR-328(P<0.05) Compared with high glucose group or miR-328 group,typeⅠ/Ⅲ collagen expressions were less pronounced after treatment with U0126.4)The expressions of p-MEK1/2 and p-ERK1/2 were increased in HUVECs treated by high glucose or miR-328 in comparison to the control group (P<0.05);a lower expression of p-MEK1/2 and p-ERK1/2 were observed in U0126 group than in high glucose group or miR-328 group.Conclusions The phenomenon of EMT in HUVECs is induced by high glucose with increased expression of miR-328;overexpression of miR-328 induced EMT in HUVECs;miR-328 induced EMT is related with MEK1/2-ERK1/2 signaling pathway.
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Objective To observe the efficacy and safety of different doses of mizoribine to prevent rejection after renal transplantation. Methods Sorted by time of operation and odevity, 206 primary kidney transplant recipients were divided into 3 groups, including MMF group, MZR Ⅰ group and MZR Ⅱ group. All recipients in 3 groups were administrated CsA and Pred, combined with mycophenolate mofitile (MMF) in MMF group and mizoribine (MMF) in MZR Ⅰ and Ⅱ groups.The dosage of MMF was 1. 0 g/day, while dosage of MZR in MZR Ⅰ and Ⅱ groups was 100 and 200 mg/day, respectively. There was no difference in usage of cyclosporine (CsA) and prednisone (Pred) among 3 groups. 100, 60 and 30 recipients were followed up in MMF, MZR Ⅰ and MZR Ⅱ groups respectively in 5 years. During the follow-up period of 5 years, the incidence of acute rejection, patient/graft survival and adverse effects associated with drugs in three groups were observed. Results The patient/graft survival was 88. 3 % (53/60), 85 % (51/60) in MZR Ⅰ group, 90 % (27/30),86.7 % (26/30) in MZR Ⅱ group, and 88% (88/100), 86% (86/100) in MMF group, respectively (P>0. 05). There was no significant difference in incidence of acute rejection among MZR Ⅰ (10 %, 6/60), MZR Ⅱ (6. 7 %, 2/30) and MMF groups (9 %, 9/100). The incidence of severe pulmonary infection in MZR Ⅰ group was 3. 3 % (2/60), and 10 % (3/30) in MZR Ⅱ , and the former was lower than MMF group (15 %, 15/100) significantly. There was significant difference in mortality of severe pulmonary infection between MZR Ⅰ group (0, 0/2) and MMT group (73. 3 %, 11/15). The rate of ACR in MZR Ⅱ group (10 %, 3/30) was lower significantly than MMF group (30 %, 30/100) and MZR Ⅰ group (31.7 %, 19/60). There was significant difference in the incidence of hyperuricacidemia between two MZR groups (30 %, 56. 7 %) and MMF group (10 %)(P<0. 05), while the incidence of diarrhea and myelosuppression was lower significantly in MZR Ⅰ group than in MMF group. Conclusion MZR can prevent acute rejection after kidney transplantation effectively and safely. Immunosuppressive therapy including mizoribine is the best choice especially for high risk group because of susceptibility to infection and those who suffer from tenacious diarrhea owing to the side effect.
ABSTRACT
Objective To detect the prevalence of hyperuricemia and its relationship to chronic kidney disease(CKD) in the residents of Guangxi, and to discuss the risk factors for the hyperuricemia associated renal damage. Methods The residents aged 18-75 years old(n=6 273) in Xiangshan community,Guilin, were screened by means of cross-sectional study. Blood pressure was measured at 8:00-9:00.Fasting blood and urine samples were collected to determine blood glucose, lipid, insulin, creatinine, and urine albumin. Results The prevalence of hyperuricemia in the community residents was 23.5% in all cohort, being significantly higher in male residents than in female(28.4% vs 19.7%,P＜0.01). The prevalence of CKD was 21.6% in all cohort, and was 24.9% in males and 19.0% in females(P＜0.01). The prevalence of CKD was 30.4% and 18.9% respectively in residents with and without hyperuricemia(P＜0.01).The prevalence of CKD in males with hyperuricemia(34.3%) was significantly higher than in males without hyperuricemia(21.2%) and females with hyperuricemia(25.9%, all P＜0.01). CKD was only positively related to low-density lipoprotein cholesterol, blood glucose, and systolic blood pressure shown by logistic regression analysis. Conclusions The prevalence of hyperuricemia markedly increases in the urban residents, which contribute to the raised prevalence of CKD. Slightly elevated blood uric acid level is associated with raised prevalence of CKD.