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黄芩苷和奥曲肽对重症急性胰腺炎多器官损伤的保护作用。

Protective effects of baicalin and octreotide on multiple organ injury in severe acute pancreatitis.

作者信息

Zhang Xi Ping, Zhang Ling, Yang Ping, Zhang Rui Ping, Cheng Qi Hui

机构信息

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

出版信息

Dig Dis Sci. 2008 Feb;53(2):581-91. doi: 10.1007/s10620-007-9868-3. Epub 2007 Jun 5.

Abstract

PURPOSE

To discuss the application value of Baicalin which is a new drug by comparing the protecting effects of Baicalin and Octreotide on multiple organs (pancreas, liver, kidney, and lung) in Severe acute pancreatitis (SAP).

METHODS

The improved Aho method was adopted to prepare SAP rat models via retrograde injection of 3.5% sodium taurocholate to the pancreatic duct. The 135 SAP rat models after being prepared were randomly divided into the model group, Baicalin treatment group and Octreotide treatment group with 45 rats in each group; another 45 were selected to be the sham operation group, which only received abdomen opening surgery. The groups were then randomly divided into 3 h, 6 h and 12 h groups with 15 rats in each group, 10 min after successful modeling, the Baicalin treatment group was first injected with a 5% Baicalin injection at a dose of 10 mg/100 g via external jugular-vein passage followed by continuous intravenous administration (10 mg/h/100 g) by microinfusion pump; the Octreotide treatment group was first injected by Octreotide at a dose of 0.2 ug/100 g via external jugular-vein passage followed by continuous intravenous transfusion (10 mg/h/100 g) by microinfusion pump at a transfusion speed of 0.2 ug/h/100 g. The sham operation group and model group were injected with saline of equivalent volume at the corresponding time points after operation. The following observations were carried out 3, 6 and 12 h after operation: (1) mortalities of all rat groups followed by batch execution of rats and observation of the gross pathological changes of multiple organs; (2) observation of the pathological changes of multiple organ samples fixed according to the relevant requirements after HE staining; and (3) serum content of amylase, NO, malonaldehyde (MDA), and tumor necrosis factor alpha (TNF-alpha).

RESULTS

(1) The survival rate of the sham operation group and all treatment groups was 100%, whilst the 12 h survival of the model group was 66.67% (10/15), indicating a significant difference (P < 0.05). (2) The gross pathological changes and changes under light microscopy of multiple organs aggravated with time after modeling. The pathological changes of all treatment groups were milder than those of the model group at different time points by various degrees, most obviously at 6 h and 12 h. The gross pathological changes showed a similarity between the Octreotide and Baicalin treatment groups in terms of the pathological changes of pancreatic tissue. The therapeutic effects of Octreotide on kidney and lung were superior to those in the Baicalin treatment group while the pathological manifestations of the Baicalin treatment group were superior to those of the Octreotide treatment group. (3) There was no marked difference between the Baicalin and Octreotide treatment groups in terms of plasma amylase levels at all time points (P > 0.05). Although the plasma amylase levels of the Baicalin treatment group were lower than those of the model group at all time points, the levels in the Baicalin treatment group were significantly lower than those in the model group only at 3 h (P < 0.05), and there was no marked difference in the levels between the Baicalin treatment group and model groups at 6 and 12 h (P > 0.05); the levels in the Octreotide treatment group were significantly lower than in the model group at 6 h (P < 0.05), and there was no marked difference between the levels in the Octreotide treatment group and model group at 3 h and 12 h (P > 0.05). (4) The serum NO contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.05), while in the Octreotide treatment group it was obviously lower than in the model group at 3 and 12 h (P < 0.01); in this regard there was no marked difference between the Baicalin and Octreotide treatment groups at different time points (P > 0.05). (5) The serum MDA contents of the Baicalin treatment group were significantly lower than those of the model group (P < 0.01), while in the Octreotide treatment group it was significantly less than the model group at 6 and 12 h (P < 0.05), and in the Baicalin treatment group was significantly less than in the Octreotide treatment group at 12 h (P < 0.05). (6) There was no marked difference among the model group, Baicalin treatment group and Octreotide treatment group in terms of serum TNF-alpha content at 3 h and 12 h (P > 0.05). At 6 h the value in the Baicalin treatment group was significantly less than in the model group (P < 0.001), in the Octreotide treatment group it was significantly less than in the model group (P < 0.001), and the Octreotide treatment group it was significantly less than in the Baicalin treatment group (P < 0.01).

CONCLUSIONS

Both Baicalin and Octreotide have obvious protective effects on the multiple organ injury in SAP with mechanisms associated to manifold factors. By comparing the pharmacologic effects of Octreotide and Baicalin, we believe that Baicalin as a new drug has a protective effect on multiple organs of a SAP rat model similar to that of Octreotide and is worth further study and development.

摘要

目的

通过比较黄芩苷与奥曲肽对重症急性胰腺炎(SAP)多器官(胰腺、肝脏、肾脏和肺)的保护作用,探讨黄芩苷作为一种新药的应用价值。

方法

采用改良的Aho法,通过向胰管逆行注射3.5%牛磺胆酸钠制备SAP大鼠模型。将制备好的135只SAP大鼠模型随机分为模型组、黄芩苷治疗组和奥曲肽治疗组,每组45只;另选45只作为假手术组,仅接受开腹手术。然后将各组随机分为3 h、6 h和12 h组,每组15只,造模成功后10 min,黄芩苷治疗组首先经颈外静脉途径注射5%黄芩苷注射液,剂量为10 mg/100 g,随后通过微量注射泵持续静脉给药(10 mg/h/100 g);奥曲肽治疗组首先经颈外静脉途径注射奥曲肽,剂量为0.2 μg/100 g,随后通过微量注射泵以0.2 μg/h/100 g的输注速度持续静脉输注(10 mg/h/100 g)。假手术组和模型组在术后相应时间点注射等量生理盐水。术后3、6和12 h进行以下观察:(1)依次处死所有大鼠组,观察多器官大体病理变化,记录死亡率;(2)对按相关要求固定的多器官样本进行HE染色后观察病理变化;(3)检测血清淀粉酶、一氧化氮(NO)、丙二醛(MDA)和肿瘤坏死因子α(TNF-α)含量。

结果

(1)假手术组和所有治疗组的存活率均为100%,而模型组12 h存活率为66.67%(10/15),差异有统计学意义(P < 0.05)。(2)建模后多器官大体病理变化和光镜下变化随时间加重。各治疗组在不同时间点的病理变化均不同程度轻于模型组,6 h和12 h时最明显。大体病理变化显示,奥曲肽和黄芩苷治疗组胰腺组织病理变化相似。奥曲肽对肾脏和肺的治疗效果优于黄芩苷治疗组,而黄芩苷治疗组的病理表现优于奥曲肽治疗组。(3)黄芩苷和奥曲肽治疗组在各时间点血浆淀粉酶水平差异无统计学意义(P > 0.05)。虽然黄芩苷治疗组各时间点血浆淀粉酶水平均低于模型组,但仅在3 h时黄芩苷治疗组水平显著低于模型组(P < 0.05),6 h和12 h时黄芩苷治疗组与模型组水平差异无统计学意义(P > 0.05);奥曲肽治疗组在6 h时水平显著低于模型组(P < 0.05),3 h和12 h时奥曲肽治疗组与模型组水平差异无统计学意义(P > 0.05)。(4)黄芩苷治疗组血清NO含量显著低于模型组(P < 0.05),而奥曲肽治疗组在3 h和12 h时明显低于模型组(P < 0.01);在此方面,黄芩苷和奥曲肽治疗组在不同时间点差异无统计学意义(P > 0.05)。(5)黄芩苷治疗组血清MDA含量显著低于模型组(P < 0.01),而奥曲肽治疗组在6 h和12 h时显著低于模型组(P < 0.05),12 h时黄芩苷治疗组显著低于奥曲肽治疗组(P < 0.05)。(6)模型组、黄芩苷治疗组和奥曲肽治疗组在3 h和12 h时血清TNF-α含量差异无统计学意义(P > 0.05)。6 h时,黄芩苷治疗组的值显著低于模型组(P < 0.001),奥曲肽治疗组显著低于模型组(P < 0.001),且奥曲肽治疗组显著低于黄芩苷治疗组(P < 0.01)。

结论

黄芩苷和奥曲肽对SAP多器官损伤均有明显保护作用,其机制与多种因素有关。通过比较奥曲肽和黄芩苷的药理作用,我们认为黄芩苷作为一种新药对SAP大鼠模型多器官具有与奥曲肽相似的保护作用,值得进一步研究和开发。

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