辛伐他汀减轻放射性唾液腺损伤的研究  

Preventive effect of simvastatin on radiation-induced salivary gland injury in mice

作　　者：许礼平[1] 杨曦[1] 赵奎领[2] 秦嗪[1] 张弛[1] 孙新臣[3] 

机构地区：[1]南京医科大学第一临床医学院,南京医学硕士研究生210029 [2]南通大学医学院,南通226001 [3]南京医科大学第一附属医院放疗科,南京210029

出　　处：《医学研究生学报》2013年第8期794-797,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81272504);江苏省科技厅基础研究计划(BK2011854)

摘　　要：目的放射性唾液腺损伤是头颈部肿瘤患者放疗后常见的并发症之一,目前尚无有效的防治措施。文中研究辛伐他汀对小鼠放射性唾液腺损伤的防治作用,并探讨其机制。方法将64只ICR小鼠随机分为对照组(模拟照射+注射溶剂)、单药组(模拟照射+注射辛伐他汀原液)、单放组(头颈部照射+注射溶剂)和联合组(头颈部照射+注射辛伐他汀原液),每组16只。给予6 MeV射线、15 Gy单次大剂量照射小鼠头颈部以构建放射性唾液腺损伤模型。照射前1周开始,单药组及联合组给予辛伐他汀溶液,按10 mg/kg体重腹腔注射给药,3次/周;对照组及单放组给予等体积溶剂腹腔注射。分别于照射后8h和4周采集小鼠唾液进行唾液定量;收集小鼠下颌腺进行MDA测定,组织学观察和Western blot法检测转化生长因子β1(transforming growth factor-β1,TGF-β1)蛋白表达量。结果联合组小鼠下颌腺组织损伤程度较单放组小鼠明显减轻。单放组小鼠照射后唾液分泌量与正常组相比8 h减少约12.7%(P<0.05),4周时减少约56.5%(P<0.01);而联合组小鼠放射后唾液量较正常组8h无明显减少(P=0.095),4周时减少约32.4%(P<0.01),显著低于单放组。放射后8h和4周,单放组下颌腺匀浆上清液中MDA含量明显高于正常组(P<0.01);联合组下颌腺匀浆上清液中MDA含量在放射8 h后较对照组显著升高(P<0.01),在4周时基本恢复至正常水平。组织学结果显示联合组下颌腺较单放组空泡变性、炎性细胞浸润及纤维化明显减轻。Western blot法检测结果显示单放组在放射后8 h及4周时TGF-β1蛋白表达量较对照组明显增加(P<0.05);而联合组表达量与对照组比较差异无统计学意义(P>0.05)。结论辛伐他汀可有效减轻小鼠放射性唾液腺损伤,有望成为一种安全有效的放射防护剂。Objective Radiation-induced salivary gland injury is one of the serious complications in patients with head and neck malignancies after radiotherapy, for which there have been no effective preventive measures. This study was to observe the preven- tive effect of simvastatin on radiation-induced salivary gland injury in mice. Methods Sixty-four ICR mice were randomly divided into a control, a simvastatin, an irradiation and a simvastatin ＋ irradiation group of equal number （ n = 16）. One week prior to irradia- tion, the mice in the irradiation and simvastatin ＋ irradiation groups were injected intraperitoneally with simvastatin at the dose of 10 mg/kg body weight 3 times a week, while those in the control and simvastatin groups received solvent only. At 8 hours and 4 weeks af- ter localized irradiation, saliva and submandibular gland tissues were collected for biochemical, morphological, and Western blot analy- ses. Results The simvastatin ＋ irradiation group exhibited obviously less injury of the submandibular gland tissue than the irradia- tion group. Compared with the controls, saliva secretion was reduced by 12.7% in the irradiation group at 8 hours （664.9 ± 33.5 vs 580±12.6, P 〈 0.05 ） and 56.5% at 4 weeks （ 678.0 ±6.9 vs 295.1 ±13.1, P 〈 0.01 ） after irradiation, but showed no obvious reduction in the simvastatin ＋ irradiation group at 8 hours （664.9 ~ 33.5 vs 662.4 ＋ 34.6, P = 0.095 ）, though a 32.4% decrease at 4 weeks （678.0±6.9 vs 458.0 ± 15.8, P 〈 0.01 ）. The MDA level was significantly higher in the irradiation than in the control group ei- ther at8 hours （12.77±0.35 vs5.93±0.23, P〈0.01） or at4 weeks （9.20 ± 0.25 vs 6.45 ± 0.29, P 〈 0.01 ）, and it was also in- creased in the simvastatin ＋ irradiation group at 8 hours but returned to normal at4 weeks （8.83 ~0.58 vs 5.93 ~0.23, P〈0.01）. Histological examination revealed less vaeuolization, inflammationinfiltration and fibrosis in the simvastatin ＋ irradiation group than in the irradiatio

关 键 词：辛伐他汀 放射防护 唾液腺 转化生长因子Β1 小鼠 

分 类 号：R972.6[医药卫生—药品]