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黄芩苷与奥曲肽对重症急性胰腺炎大鼠肾损伤的保护作用及机制

Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis.

作者信息

Zhang Xi-Ping, Tian Hua, Lai Yue-Hong, Chen Li, Zhang Ling, Cheng Qi-Hui, Yan Wei, Li Yun, Li Qing-Yu, He Qing, Wang Fei

机构信息

Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang University School of Medicine, China.

出版信息

World J Gastroenterol. 2007 Oct 14;13(38):5079-89. doi: 10.3748/wjg.v13.i38.5079.

Abstract

AIM

To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP).

METHODS

One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-alpha, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation.

RESULTS

The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P<0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P<0.01, 29.200+/-5.710 micromol/L vs 38.400+/-11.344 micromol/L; P<0.05, 33.533+/-10.106 micromol/L vs 45.154+/-17.435 micromol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P<0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P<0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P<0.05, 57.50 (22.50) and 52.50 (15.00) micromol/L vs 65.00 (7.50) micromol/L; P<0.01, 57.50 (27.50) and 45.00 (12.50) micromol/L vs 74.10 (26.15) micromol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-alpha (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P<0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91+/-20.61 and 66.86+/-22.10 U/mL, 63.13+/-26.31 and 53.63+/-12.28 U/mL vs 101.46+/-14.67 and 105.33+/-18.10 U/mL, respectively].

CONCLUSION

Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.

摘要

目的

探讨黄芩苷和奥曲肽对重症急性胰腺炎(SAP)大鼠肾损伤的保护作用及机制。

方法

将180只SD大鼠随机分为模型组、黄芩苷治疗组、奥曲肽治疗组和假手术组。观察术后3、6和12 h时的死亡率、血浆内毒素水平、血清中血尿素氮(BUN)、肌酐(CREA)、磷脂酶A2(PLA2)、一氧化氮(NO)、肿瘤坏死因子(TNF)-α、白细胞介素-6(IL-6)和内皮素-1(ET-1)的含量、肾组织Bax和Bcl-2蛋白表达水平、凋亡指数及肾脏病理变化。

结果

治疗组肾脏病理改变较模型组轻。治疗组12 h生存率及6 h肾凋亡指数显著高于模型组(P<0.05)[分别为66.67%对100%;0.00(0.02)%和0.00(0.04)%对0.00(0.00)%]。奥曲肽治疗组3 h和6 h时血清CREA含量显著低于模型组(P<0.01,29.200±5.710 μmol/L对38.400±11.344 μmol/L;P<0.05,33.533±10.106 μmol/L对45.154±17.435 μmol/L)。模型组与各治疗组在各时间点肾Bax蛋白表达水平差异均无统计学意义。黄芩苷治疗组6 h时肾Bcl-2蛋白表达水平低于模型组[P<0.001,0.00(0.00)分级评分对3.00(3.00)分级评分]。奥曲肽治疗组6 h和12 h时Bcl-2表达水平低于模型组[P<0.05,0.00(0.00)分级评分对3.00(3.00)分级评分;0.00(0.00)分级评分对0.00(1.25)分级评分]。治疗组3 h和12 h时血清NO含量低于模型组[P<0.05,57.50(22.50)和52.50(15.00)μmol/L对65.00(7.50)μmol/L;P<0.01,57.50(27.50)和45.00(12.50)μmol/L对74.10(26.15)μmol/L]。治疗组血浆内毒素含量及血清BUN含量(6 h和12 h时)低于模型组。治疗组IL-6、ET-1、TNF-α(6 h时)和PLA2(6 h和12 h时)含量低于模型组[P<0.001,3.031(0.870)和2.646(1.373)pg/mL对5.437(1.025)pg/mL;2.882(1.392)和3.076(1.205)pg/mL对6.817(0.810)pg/mL;2.832(0.597)和2.462(1.353)pg/mL对5.356(0.747)pg/mL;16.226(3.174)和14.855(5.747)pg/mL对25.625(7.973)pg/mL;18.625(5.780)和15.185(1.761)pg/mL对24.725(3.759)pg/mL;65.10(27.51)和47.60(16.50)pg/mL对92.15(23.12)pg/mL;67.91±20.61和66.86±22.10 U/mL,63.13±(26.31)和53.63±12.28 U/mL对101.46±14.67和105.33±18.10 U/mL]。

结论

黄芩苷和奥曲肽均可保护重症急性胰腺炎大鼠的肾脏。黄芩苷和奥曲肽的治疗机制可能与其抑制炎症介质及诱导凋亡有关。黄芩苷可能是治疗重症急性胰腺炎的一种有前景的治疗手段。

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