摘要
目的探讨红景天对大鼠重症急性胰腺炎相关性肾损伤的保护作用及机制。方法将健康SD大鼠90只随机分为:假手术组(S组)、重症急性胰腺炎相关性肾损伤组(M组)、低剂量治疗组(3g/kg,T1组)、中剂量治疗组(6g/kg,T2组)、高剂量治疗组(9g/kg,T3组)。S组和M组在建模前3h予以6g/kg的生理盐水腹腔注射,各剂量治疗组建模前3h大鼠分别予以3g/kg、6g/kg、9g/kg红景天注射液腹腔注射。M组和治疗组开腹后钝性分离胰腺周围韧带至胰头部,无创血管钳夹闭胰头3h后松开关腹后建立模型。在造模完成后各组分别于12h、24h、36h随机取6只大鼠检测血淀粉酶、肌酐、尿素氮。采用酶联免疫吸附试验(ELISA)检测大鼠血清IL-1β、IL-10含量,再取左肾组织行病理组织学观察;右肾行超氧化酶(SOD)活性测定及实时定量聚合酶链反应(RT-PCR)检测缺氧诱导因子-1α(HIF-1α mRNA的表达量。结果与假手术比较,各时间点M组的血清淀粉酶活性、肌酐、尿素氮浓度及IL-1β值均显著升高,但SOD的活性明显下降。T2组与M组比较,各时间点T2组的血清淀粉酶活性、肌酐、尿素氮浓度及IL-1β值均显著下降(P〈0.05),但SOD活性、IL—10值、HIF-1α mRNA表达量明显升高,差异有统计学意义(P〈0.05)。与T1组比较,随着药物浓度的增加,他组肾脏和胰腺功能在各时间点均有相对更好的表现,差别有统计学意义。但T3组与他组比较,随着红景天药物浓度的进一步增加,大鼠的各项检测指标无明显改善,差别无统计学意义(P〉0.05)。结论中浓度(6g/kg)的红景天注射液对大鼠重症急性胰腺炎相关性肾损伤有较好的保护作用。红景天对重症急性胰腺炎相关性肾损伤的治疗作用可能与抑制IL-1β表达,上调IL-10、HIF-1α mRNA表达以及提高SOD活性,从而减少肾脏细胞凋亡及坏死,提高肾脏耐缺氧的能力有关。
Objective To investigate the effect of rhodiola on severe acute pancreatitis associated renal injury and explore the potential mechanisms. Methods A total of 90 rats were randomly divided into sham-operated group (S group, n = 18), severe acute pancreatitis with renal injury group (M group, n = 18), low rhodiola dose group (3 g/kg, T1 group, n = 18), moderate dose rhodiola group (6 g/kg, T2 group, n=18), high rhodiola dose group (9 g/kg, T3 group, n = 18). The S and M groups were given 6 g/kg saline through intraperitoneal injection before operation while the T1 group, T2 group and T3 group were given with 3 g/kg, 6 g,/kg, 9 g/kg dose of rhodiola through intraperitoneal injection, respectively. The pancreas was dissected and the head of pancreas was occluded by blood vessel forceps for 3 hours to make rat model. All the rats were sacrificed at 12 h, 24 h, 36 h after modeling. The level of ascites amylase, serum amylase, creatinine, blood urea nitrogen, interleukin 1β( IL-1β) and interleukin 10 (IL-10) were detected and the pathological change of pancreas and the left kidney was observed under light microscope. The serum levels of IL-1β and IL-10 were detected by enzyme-linked immunosorbert assay (ELISA). Take the right kidney for superoxide dismutase (SOD) determination and the expression of hypoxia inducible factor-1α(HIF-1α)mRNA in the right kidney was detected by real-time polymerase chain reaction (RT-PCR). Results Compared with the S group, the level of serum amylase, creatinine, blood urea nitrogen and IL-1 [3 in M group increased significantly, but the activity of SOD has a significant decline (P 〈0. 05). Compared with M group, the level of serum amylase, creatinine, blood urea nitrogen and IL-1β in T2 group has a significant decline, but the activity of SOD, the express of HIF-1α mRNA and IL-10 has a significant increase ( P 〈 0. 05 ). With the dose of rhodiola increased, the renal and pancreatic function in T2 group had a better performance than T1 group, and the difference was statistical significant (P 〈 0. 05). But compared with T2 group, the renal and pancreatic function in T3 group did not increased significantly (P 〉 0. 05 ). Conclusions Moderate dose of rhodiola (6 g/kg) has a good protective effect on severe acute pancreatitis associated renal injury. It may be associated with the inhibitory expression of IL-1β, up-regulated expression of IL-10, HIF-1α mRNA, and the increased activity of SOD. So it can then reduce cell apoptosis and renal necrosis, and improve the ability of the kidney to tolerate hypoxia.
出处
《中华肝胆外科杂志》
CAS
CSCD
北大核心
2014年第6期461-466,共6页
Chinese Journal of Hepatobiliary Surgery
基金
中国博士后科学基金(20100481517)
关键词
重症急性胰腺炎
肾损伤
红景天
缺氧诱导因子-1Α
Severe acute pancreatitis
Renal injury
Rhodiola
Hypoxia inducible factor-1α (HIF-1α)