姜黄素联合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

Protective and Therapeutic Effects of Curcumin Combined with Rhodiola on Rats with Severe Acute Pancreatitis Associated Renal Injury

目的探讨姜黄素联合红景天对大鼠重症急性胰腺炎(SAP)相关性肾损伤的保护作用及机制。方法将健康SD大鼠24只按随机数字表法分为SAP相关性肾损伤组(简称"SAP组")、姜黄素治疗组(简称"姜黄素组")、姜黄素联合红景天治疗组(简称"姜黄素+红景天组"),每组8只。SAP组在建模前3 h予以大鼠1.5 m L的生理盐水腹腔注射,姜黄素组建模前3 h予以大鼠200 mg/kg的1.5 m L姜黄素稀释液灌胃,姜黄素+红景天组建模前3 h同时予以大鼠200 mg/kg的1.5 m L姜黄素稀释液灌胃和6 g/kg的红景天注射液腹腔注射。各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3 h后松开,关腹。在造模完成后每组于18 h按随机数字表法取8只大鼠取材,然后检测其血淀粉酶、肌酐、尿素氮。采用酶联免疫吸附试验检测大鼠血清白介素(IL)-1β、IL-6和IL-10含量,再取左肾组织行病理组织学观察及采用TUNEL染色法检测细胞凋亡情况;右肾组织行实时定量聚合酶链反应检测诱生型一氧化氮合酶(i NOS)m RNA表达水平;采用羟胺法测定肾组织中超氧化物歧化酶(SOD)活性。结果 SAP组的血淀粉酶活性、肌酐、尿素氮浓度及IL-1β、IL-6水平、细胞凋亡指数、i NOS m RNA的表达量均明显高于姜黄素组(P<0.05),而SOD活性和IL-10水平明显低于姜黄素组(P<0.05)。与姜黄素组相比较,姜黄素+红景天组的肾脏和胰腺功能具有更好的表现,姜黄素+红景天组的IL-1β、IL-6水平、细胞凋亡指数、i NOS m RNA的表达量均明显降低(P<0.05),而SOD活性和IL-10水平明显升高(P<0.05)。结论姜黄素联合红景天对大鼠SAP相关性肾损伤有较好的治疗作用,这种治疗作用主要通过抑制促炎性因子IL-1、IL-6的表达,促进抗炎性因子IL-10表达和提高SOD活性,下调i NOS m RNA的表达,从而减少肾脏的细胞凋亡及坏死。

Objective To investigate the effect of Curcumin combined with Rhodiola on rats with severe acute pancreatitis （SAP） associated renal injury and explore the possible mechanisms. Methods A total of 24 rats were randomly divided into SAP with renal injury group （SAP group, n=8）, Curcumin group （n=8）, Curcumin combined with Rhodiola group （n=8）. The SAP group was given 1.5 mL saline through intragastric administration before operation while the Curcumin group was fed with same amount of Curcumin diluent. The Curcumin combined with Rhodiola group was given 1.5 mL Curcumin diluent through intragastric administration and 6 g/kg Rhodiola diluent through intraperitoneal injection before operation. The pancreas and pancreatic tail-segment was dissociated and the head of pancreas were occluded in rats to make the model, blood vessel forceps was loosed after three hours. All the rats were sacrificed at 18 h after modeling. The levels of serum amylase, creatinine, blood urea nitrogen were detected and pathological changes of pancreas and the left kidney were observed under the light microscope. The cell apoptosis was analyzed using TUNEL staining. The serum levels of interleukin （IL） -1β, IL-6, and IL-10 among the three groups were detected by enzyme-linked immunosorbent assay. The expression of inducible nitric oxide synthase （iNOS） mRNA in the right kidney was detected by real-time polymerase chain reaction. The superoxide dismutase （SOD） activity of the renal tissue was determined by hydroxylamine method. Results Compared with the SAP group, the levels of serum amylase, creatinine, blood urea nitrogen, IL-1β, IL-6, the cell apoptosis index, and the expression of iNOS mRNA were significantly decreased, the serum level of IL-10 and the activity of SOD were significantly increased （P〈 0.05）, the pancreas and the kidney damaged more slightly in the Curcumin group and Curcumin combined with Rhodiola group. Compared with the Curcumin group, the above situations were more better in the Curcumin combined with Rhodiola group. Conelusions Curcumin combined with Rhodiola has a better protective effect on SAP associated renal injury. It might be through inhibiting the expressions of IL-1β, IL-6, stimulating the expression of IL-10, down-regulating the expression of iNOS mRNA, and improving the activity of SOD. It could reduce the cell apoptosis and necrosis of the kidney and improve the ability of the kidney to tolerate hypoxia.