氟伐他汀及缬沙坦对糖尿病肾病相关炎症因子的影响

Comparison of the effects of fluvastatin and valsartan on the inflammatory cytokines in patients withdiabetic nephropathy

目的比较氟伐他汀及缬沙坦对2型糖尿病早期肾病相关炎症因子的影响及对糖尿病肾病的保护作用。方法2型糖尿病早期。肾病共90例，其中常规降糖治疗组作为对照组（DNl组），在常规降糖治疗基础上加用缬沙坦作为缬沙坦组（DN2组），在常规降糖治疗基础上加用氟伐他汀作为氟伐他汀组（DN3组）。分别测定各组患者治疗前后的血糖、血脂、血肌酐（SCr）、C反应蛋白（CRP）、24h尿蛋白定量、尿白蛋白排泄率（UAER）及数种炎症因子。结果（1）干预前3组的血清CRP、转化生长因子．B1（TGF．131）、白细胞介素-6（IL-6）、肿瘤坏死因子．仪（TNF-仅）、白细胞介素一18（IL一18）浓度差异无统计学意义。DN2组治疗后与治疗前相比，IL-6[（15．99±2．87）ng／L与（17．64±2．91）ng／L，t=一3．091，P〈0．01]、TNF-仪[（48．72±14．62）ng／L与（52．56±17．02）ng／L，t=一2．131，P〈0．05]、TGF-B1[（33．54±10．69）μg/L与（40．11±12．08）μg/L，t=一2．921，P〈0．01]、IL-18[（139．65±66．37）ng／L与（158．74±74．20）ng／L，t=一2．053，P〈0．05]、CRP[（5．12±3．54）mg／L与（6．08±3．39）mg／L，t=一2．072，P〈0．05]均明显降低；DN3组治疗后与治疗前相比，IL-6[（15．39±2．77）ng／L与（16．49±2．81）ng／L，t=一2．071，P〈0．05]、TNF—α{[（45．89±16．22）ng／L与（53．04±17．02）ng／L，t=一3．651，P〈0．01]、TGF-B1[（31．19±10．48）μg/L与（37．11±11．76）μg/L，t=一2．963，P〈0．01]、IL一18[（141．54±66．65）ng／L与（158．01±73．23）ng／L，t=一2．182，P〈0．05]、CRP[（4．94±3．61）mg／L与（5．86±3．46）mg／L，t=一2．110，P〈0．05]亦均明显降低。DN2、DN3组治疗后的炎症因子含量差异无统计学意义（P〉0．05）。（2）在DN2、DN3组治疗前后血压均无差异情况下，DN2组治疗后与治疗前比较，UAER[（63．1±31．7）斗g／rain与（82．9±40．0）肌g／min，t=一2．145，P〈0．05]、24h尿蛋白定量[（0．14±0．11）g／24h与（0．18±0．15）g/24h，t=一2．438，P〈0．05]、尿微量白蛋白／肌酐（ALb／Cr）[（114．7±68．1）mg／g与（162．0±83．8）mg／g，t=一2．399，P〈0．05]均明显降低，DN3组治疗后与治疗前比较，UAER[（65．5±32．6）μg／min与（83．5±42．1）μg／min，t=一2．131，P〈0．05]、24h尿蛋白定量[（0．15±0．12）g／24h与（0．18±0．13）g／24h，t=一2．611，P〈0．05]、尿ALb／Cr[（119．1士78．2）mg／g与（160．0l±82．3）mg／g，t=一2．213，P〈0．05]亦均明显降低，但2组治疗后结果比较差异均无统计学意义（P均〉0．05）。结论2型糖尿病肾病患者用缬沙坦、氟伐他汀均能降低尿蛋白，降低相关血清炎症因子含量，提示对肾功能具有保护作用。

Objective To compare the effects of fluvastatin and vaisartan on me lmiammatory cytotcmes in the early stage of type 2 diabetic nephropathy and their protective effects on to diabetic nephropathy. Methods Ninety patients with early stage of type 2 diabetic nephropathy were divided into three groups, 30 patients receiving routine hypoglyccmic agents （DN1） as control ,30 patients receiving routine hypoglycemic agents plus valsartan （DN2） and the other 30 receiving routine hypoglycemie agents plus fluvastatin （ DN3 ）. Blood glucose, blood lipid, serum creatinine and C reactive protein（CRP） ,24-hour urine protein, urinary albumin excretion rate （UAER） and several inflammatory cytokine were measured before and after treatment. Results （1）No significant difference of the levels of serum CRP, TGF-IM, IL-6, TNF-ot, IL-18 at the baseline were observedamong these three groups. In the DN2 group, after treatment, IL-6 was （ [ 15.99±2. 87 ] ng/L and [ 17.64 ±2.91 ] ng/L,t = - 3. 091, P 〈 0.01 ）, TNF-α was （ [ 48. 72 ± 14. 62 ] ng/L -与 [ 52. 56 ＋ 17.02 ] ng/L, t = - 2. 131, P 〈 0. 05 ）, TGF-131 was （ [ 33.54 ± 10. 69 ] μg/L and [ 40. 11 ± 12.08 ] μg/L, t = - 2. 921, P 〈 0. 01 ）, IL-18 was （ [ 139. 65±66. 37] ng/L and [ 158. 74±74. 20] ng/L,t = -2. 053 ,P 〈0.05） ,CRP was （ [5.12 ± 3.54] mg/L and [ 6. 08 ± 3.39 ] mg/L, t = - 2. 072, P 〈 0.05 ） after and before treatment, respectively. All abovemented indices significantly decreased after treatment. In the DN3 group, IL-6 was （ [ t5.39 ± 2. 77 ] ng/L and [ 16.49 ± 2. 81 ] ng/L, t = - 2. 071, P 〈 0. 05 ）, TNF-α was （ [ 45.89 ± 16.22 ] ng/L 与 [ 53.04 ± 17.02 ] ng/L,t = -3.651, P 〈 0. 01 ）, TGF-I31 was （ [ 31.19± 10. 48 ] μg/L and [ 37.11 ± 11.76 ] μg/L, t = - 2. 963, P〈0. 01） ,IL-18 was （[141.54 ± 66. 65]ng/L and [158.01 ±73.23]ng/L,t = -2. 182,P 〈0.05）,CRP （[4.94± 3.61] mg/L -与 [5.86 ± 3.46] mg/L, t = - 2. 110, P 〈 0.05） before and after treatment, respectively. All abovemented indices significantly decreased after treatment. No significant difference was observed on inflamaory factors after treatment between the DN2 and DN3 group （ P 〉 0. 05 ）. （2） In the subgroup that there was no difference in blood pressure between before and after treatment in both the DN2 and DN3 group,in the DN3 group, UAER was （ [ 63.1± 31.7 ] μg,/min and [ 82. 9 ± 40.0 ]μg/min, t = - 2. 145, P 〈 0. 05） ,24 h total urokinase protein was （ [0. 14± 0. 11 ] g/24 h and [ 0. 18 ± 0. 15 ] g/24 h, t = - 2. 438, P 〈 0.05 ）, microalbuminuria/urine creatinine was （ [ ALb/Cr ] [ 114. 7± 68. 1 ] mg/g and [ 162. 0± 83.8 ] mg/g, t = - 2. 399, P 〈 0.05 ） after and before treatment. All abovemention indices significantly decreased after treatment. In the DN3 group,UAER was （[65.5±32. 6] μg/min and [83.5 ±42. 1 ] μg/min,t = -2. 131 ,P 〈 0. 05 ）, 24 h total urine protein was （ [ 0. 14 ＋ 0. 11 ] g/24 h and [ 0. 18 ± 0. 15 ] g/24 h, t = - 2. 438, P 〈 0. 05 ）, microalbuminuria/＇urine creatinine was （ [ 114. 7 ＋ 68.1 ] mg/g -与 [ 162. 0 ±83.8 ] rag/g, t = - 2. 399, P 〈 0. 05 ） after and before treatment. All abovemention indices significantly decreased after treatment. No significant difference was observed after treatment between the DN2 and DN3 group （ P 〉 0. 05 ）. Conclusion Both valsartan and fluvastatin are able to protect the renal function of patients with type 2 diabetic nephropathy by decreasing the levels of urine proteins and correlated serum inflammatory cytokines.