生长抑素及Octreotide对急性胰腺炎胰腺细胞凋亡的作用机制

目的 :探讨生长抑素 (SS)及其类似物 (Octreotide)治疗小鼠急性胰腺炎对胰腺细胞凋亡及凋亡调控基因 bax、p5 3的作用。方法 :以雨蛙肽诱导 CD 1小鼠急性胰腺炎模型 ,并应用细胞凋亡原位标记检测(TU NEL)染色、免疫组化技术等检测胰腺细胞凋亡及凋亡调控基因 bax、p5 3的蛋白表达 ,以及生长抑素及其类似物治疗后对胰腺细胞凋亡及凋亡调控基因 bax和 p5 3蛋白表达的影响。结果 :HE染色见胰腺组织中典型的细胞核固缩及凋亡小体形成。 SS治疗后 1小时及 Octreotide治疗后 5、14小时胰腺细胞凋亡指数显著高于非治疗组 1、5和 14小时各时间点 (P均 <0 .0 1)。正常胰腺组织未见凋亡调控基因 bax、p5 3的表达 ,SS治疗后1小时胰腺细胞 p5 3染色阳性率明显高于非治疗组 ,P<0 .0 1,而非治疗组和 SS治疗组 1小时的胰腺细胞 bax染色阳性率无显著差异 ;Octreotide治疗后 5、14小时胰腺细胞 bax染色阳性率明显高于非治疗组相应时间点 ,P均 <0 .0 1,而非治疗组和 Octreotide治疗组 5、14小时的胰腺细胞 p5 3染色阳性率无显著差异。结论 :生长抑素及其类似物治疗急性胰腺炎的相同机制之一可能是诱导损伤的胰腺细胞凋亡以减轻炎症反应 ,但前者诱导胰腺细胞凋亡机制可能与凋亡调控基因 p5 3的表达有关而与 bax的表达无关 ;

肿瘤生长抑素受体显像剂^(99)Tc^m-octreotide的制备及鉴定

目的 建立99Tcm 直接标记octreotide的最佳方法 ,评价其受体介导结合特性以及作为肿瘤生长抑素受体显像剂的可能性。方法 采用抗坏血酸钠和连二亚硫酸钠作为还原剂 ,对oct reotide进行标记 ;用大鼠脑皮质细胞膜进行体外受体结合分析 ;进行动物体内分布、药代动力学、毒性实验和临床受体显像。结果 99Tcm octreotide放化纯达 78 5 % ,纯化后为 93 8% ,室温下放置 4h为92 1%。细胞膜体外放射受体结合分析证实99Tcm octreotide与octreotide具有相同的受体介导结合特性。 3例肺癌患者临床受体显像均获得阳性结果。结论 99Tcm 直接法标记octreotide方法可行 ,稳定性好 ;99Tcm

^(99)Tc^m直接法标记Octreotide

建立了 99Tcm直接标记 Octreotide的方法 ,并选出了最佳标记条件。在最佳标记条件下 ,标记率为 78.6 % ,纯化后放化纯度为 93.8%。纯化后的标记物室温下放置 4 h,或分别与过量 DTPA、HSA和 L-半胱氨酸 37℃孵育 4 h,其放化纯度为 92 .1%～ 93.6 % ,无显著改变。 99Tcm 直接标记Octreotide方法可行 ,标记肽稳定性好 ,可望用于生长抑素受体显像。

NCI-H446细胞的^(125)Ⅰ-[Tyr^3]octreotide受体分析

目的 :探讨小细胞肺癌与 [Tyr3 ]octreotide (TOC)的亲和力。方法 :用氯胺T方法标记的12 5I-TOC作为配基 ,检测小细胞肺癌细胞株NCl-H4 4 6与其结合的受体位点数及亲和常数。结果 :氯胺T法标记的12 5I-TOC经SephadexG - 10纯化后放化纯大于 95 % ;受体分析显示NCI-H4 4 6表达的生长抑素受体多 (Bmax =1 17× 10 5受体位点 /细胞 ) ,与12 5I-TOC亲和力强 (Kd =0 5 8nM)。结论 :TOC的标记物可用于小细胞肺癌肿瘤的受体显像及放射治疗。

Octreotide的^(131)I标记及Graves眼病炎症细胞的体外摄取

将octreotide中的苯丙氨酸用酪氨酸替换合成[Tyr3]octreotide,对其进行了131I标记。考察了氯胺T标记法中氯胺T和[Tyr3]octreotide的用量对标记率的影响,观察了Graves眼病相关炎症细胞对131I-[Tyr3]octrotide的体外摄取情况。结果表明,对octreotide进行结构修饰后得到的[Tyr3]octreotide可以用于131I标记;氯胺T法对[Tyr3]octreotide进行131I标记时,氯胺T和[Tyr3]octreotide的最佳用量分别为1.6和1.4μg,最高标记率为85%;T淋巴细胞、活化的成纤维细胞及血管内皮细胞均能够摄取131I-[Tyr3]octreoti-de,而脂肪细胞的摄取则明显较少。以上结果表明,131I-[Tyr3]octreotide能够被Graves眼病发病过程中的炎症细胞摄取,具有用于Graves眼病发病过程中炎症反应程度评估的应用潜力。但由于摄取量还很小,需要进一步深入研究。

^(188)Re直接标记octreotide的方法学

188Re标记octreotide可用直接标记法或间接标记法。直接标记法包括预锡化法和分步还原法,分步还原法需先用还原剂还原octreotide,然后用SnCl2还原188ReO4-进行直接标记;预锡化法则直接以SnCl2还原octreotide和188ReO4-,打开octreotide分子内双硫键,使188Re直接标记octreotide。预锡化直接标记法简便快速,能够得到较高的放化纯度,无须进一步纯化,适合用于制备药盒。

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

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)-α, 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 μmol/L vs 38.400 ± 11.344 μmol/L; P < 0.05, 33.533 ± 10.106 μmol/L vs 45.154 ± 17.435 μmol/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) μmol/L vs 65.00 (7.50) μmol/L; P < 0.01, 57.50 (27.50) and 45.00 (12.50) μmol/L vs 74.10 (26.15) μmol/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-α (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.

Effects of octreotide on acute necrotizing pancreatitis in rabbits

AIM:To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis,and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS:Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b.m,of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct.Sham- operated animals served as control.Octreotide i mg/kg·b.m. was administered subcutaneously before the induction of pancreatitis.Blood was taken from the jugular vein before and at 1,3,6,12 and 24 h after pancreatitis induction. Serum activities of amylase,IL-6 and TNF-α and levels of malonyl dialdehyde (MDA),glutathione (GSH),glutathione peroxidase (GPx),catalase and superoxide dismutase (Mn-, Cu-,and Zn-SOD) in pancreatic tissue were measured. RESULTS:Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis,and then returned to control level.The tissue concentration of MDA was significantly elevated at 24 h,while the GSH level and GP-x,catalase,Mn-SOD,Cu-,Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control.Octreotide pretreatmnent significantly reversed the changes in cytokines and reactive oxygen metabolites.Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. CONCLUSION:Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits.Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites,but does not have any beneficial effects on the development of necrotizing pancreatitis.

Naloxone or Vagotomy Does Not Influence Centrally Octreotide-induced Inhibition of Gastric Acid Secretion in Rats

Summary： To investigate the effect of preceding naloxone injection into the third cerebroventricle or acute subdiaphragmatic vagotomy on the gastric acid secretion inhibited by the somatostatin analogue octreotide given by intracerebroventricular （icv） injection. The third ventricles were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later, acute gastric lumen perfusion was carried out. The gastric perfusion samples were collected every 10 min and were titrated by 0.01 mol/L NaOH to neuter. On the basis of subcutaneous injection of pentagastrin （G-5, 160 g/kg）, icv injection of physiological saline （group A, n=20）, icv injection of octreotide （0.05 μ g） （group B, n=20）, icv injection of naloxone （2.5 μ g）＋octreotide （0.05 μg） （group C, n=20）, acute subdiaphragmatic vagotomy＋ icv injection of physiological saline （group D, n=20）, or acute subdia- phragrnatic vagotomy＋icv injection of octreotide （0.05 μg） （group E, n=20） were conducted. Before and after icv injection, 1-h total acid output （TAO） was determined and compared. The experimental data were expressed in change rate （%） of TAO. The change rates （%） of TAO were 4.60 % in group A, -20.35 % in group B, - 18.06 % in group C, 5.01% in group D and -21.59 % in group E, respectively. Comparison of group B or C versus group A showed that P〈0.01 and comparison between the group E versus group D showed that P〈0.01. Whereas the differences between group C and group B, group E and group B were not statistically significant （P〉0.05 for all）. The results indicate that the central inhibition of gastric acid secretion by octreotide may not be mediated by the endogenous opi- ate substance or its receptor and the peripheral pathway for icv injection of octreotide to suppress gastric acid secretion is via extra-vagus route.

Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: Randomized placebo-controlled trial

AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

Study on protecting effects of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and Octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and Octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic indexes.RESULTS: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and Octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.

非小细胞肺癌荷瘤鼠^(99m)Tc-acetate-octreotide显像与生长抑素受体表达水平的实验研究

目的:探讨非小细胞肺癌(NSCLC)荷瘤鼠模型肿瘤组织中生长抑素受体(SSTR)的表达水平与99mTc-acetate-octreotide显像的相关性研究。方法:体外培养NSCLC细胞株SPC-A1,种植于balb/c裸鼠皮下成瘤,建立人NSCLC荷瘤鼠模型;行99mTc-acetate-octreotide显像,勾画ROI计算肿瘤与对侧正常组织(N/NT)放射性比值,并测定肿瘤及主要脏器单位组织的放射性摄取百分值(%ID/g),采用逆转录-聚合酶反应(RT-PCR)检测肿瘤组织中各SSTR亚型mRNA的表达水平,对SSTR亚型表达水平与T/NT放射性摄取比值进行相关性研究。结果:99mTc-acetate-octreotide NSCLC荷瘤鼠模型显像示肿瘤部位有较高的放射性浓聚,与对侧正常组织T/NT比值较高,4h达2.38±0.09;99mTc-acetate-octreotide荷瘤鼠体内生物学分布示药物在肿瘤部位有较高的摄取;RT-PCR示NSCLC组织中有着丰富的SSTR表达,SSTR3、SSTR5亚型表达水平较高,其中SSTR5的mRNA表达水平与肿瘤显像阳性荷瘤鼠T/NT比值呈正相关(r=0.93,P<0.01)。结论:NSCLC细胞株SPC-A1高表达SSTR3和SSTR5,其中SSTR5表达水平与肿瘤组织对99mTc-acetate-octreotide的摄取呈正相关。99mTc-acetate-octreotide受体显像对NSCLC有较好的影像诊断价值。

Octreotide ameliorates gastric lesions in chronically mild stressed rats

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for CMS.Octreotide was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress procedure.Macro-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed histopathologically.Moreover,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,P<0.001),prostaglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose levels.These beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.

Octreotide induces caspase activation and apoptosis in human hepatoma HepG2 cells

AIM: To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (HepG2) cells. METHODS: We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of HepG2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method. RESULTS: After an initial increase in HepG2 cellular proliferation, a significant inhibition was observed with 10-8 mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. Octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α signifi cantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10-8 mol/L, while lower concentrations increased proliferation. CONCLUSION: Our findings are suggestive of caspasemediated signaling pathways of octreotide antitumor activity in HepG2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations.

Efficacy of octreotide in the prevention of complications after pancreaticoduodenectomy in patients with soft pancreas and non-dilated pancreatic duct: A prospective randomized trial

Background: The efficacy of octreotide to prevent postoperative pancreatic fistula(POPF) of pancreaticoduodenectomy(PD) is still controversial. This study aimed to evaluate the effect of postoperative use of octreotide on the outcomes after PD.Methods: This is a prospective randomized controlled trial for postoperative use of octreotide in patients undergoing PD. Patients with soft pancreas and pancreatic duct < 3 mm were randomized to 2 groups.Group I did not receive postoperative octreotide. Group II received postoperative octreotide. The primary end of the study is to compare the rate of POPF.Results: A total of 104 patients were included in the study and were divided into two randomized groups.There were no significant difference in overall complications and its severity. POPF occurred in 11 patients(21.2%) in group I and 10(19.2%) in group II, without statistical significance(P = 0.807). Also, there was no significant differences between both groups regarding the incidence of biliary leakage(P = 0.083), delayed gastric emptying(P = 0.472), and early postoperative mortality(P = 0.727).Conclusions: Octreotide did not reduce postoperative morbidities, reoperation and mortality rate. Also, it did not affect the incidence of POPF and its clinically relevant variants.

Effects of octreotide on glucose transporter type 2expression in obese rat small intestine

AIM： TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 （GLUT2） in obese rat intestinal mucosa. METHODS： We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention （：jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee＇s index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS： Body weight, Lee＇s index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group （605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01）. Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats （508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05）. The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group （269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01）. CONCLUSION： High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.

Effects of octreotide on gallbladder pressure and myoelectric activity of Oddi sphincter in rabbits

AIM To observe the effect of octreotide (OT) and somatostatin (SS) on gallbladder pressure and myoelectric activity of SO in rabbits. METHODS Male rabbits fasted for 15h - 18h and anesthetized with urethane. The mean gallbladder pressure (GP) and myoelectric activity of SO were simultaneously measured with a frog bladder connected to a transducer and a pair of copper electrodes. RESULTS After injection of OT (10μg/kg, iv), the GP decreased in 2min and reached the lowest value in about 60min ( P <0 01, n =19), and completely or partially returned to the normal level in 120min. The frequency of myoelectric activity of SO was reduced, even disappeared in 2min ( P <0 01, n =19) and returned to normal in about 20min . Injection of SS (10μg/kg, iv) also decreased GP and myoelectric activity of SO ( P <0 01, n =7); Before and after injection of OT or SS, injection of CCK 8 ( 100ng or 200ng ) caused similar increase in myoelectric activity of SO and GP ( P >0 05). Before and after injection of OT, there were no significant differences in increases of myoelectric activity of SO and GP caused by electric stimulation of dorsal motor nucleus of vagus ( P >0 05). CONCLUSION OT and SS decreased GP and myoelectric activity of SO, demonstrating that effects of OT were similar to those of SS. Intravenous injection of OT did not affect the increase of myoelectric activity of SO and GP caused by CCK 8 or electric stimulation of dorsal motor nucleus of vagus.

Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and octreotide

BACKGROUND: Severe acute pancreatitis (SAP) features fatal pathogenetic conditions and high mortality rate. The study of SAP complicated with multiple organ injuries is of important significance. In this study, we explored the protective effect of baicalin on multiple organs of SAP rats and compared it with that of octreotide through light and electron microscopic observations of the pathological changes. METHODS: The improved Aho method was used to prepare SAP rat models. These rats were then randomly divided into a sham-operated group (n=45), a model control group (n=45), baicalin-treated group (n=45) and octreotide-treated group (n=45). Based on the difference in time points after operation, these groups were subdivided into 3, 6 and 12 hour subgroups (n=15). At the corresponding time point after operation, the mortality rate of rats was recorded, and then the rats were humanely killed to take samples of multiple organs that were subsequently examined for pathological changes under light and electron microscopy. RESULTS: At 12 hours after operation, the mortality rate of rats in the baicalin- and octreotide-treated groups was lower than that in the model control group (P < 0.05). Compared to the model control group, the pathological changes and pathological scores in the baicalin- and octreotide-treated groups were mitigated and relieved to varying degrees. The pathological changes under electron microscopy were also improved. CONCLUSIONS: Both baicalin and octreotide show good protective effects on multiple organs of SAP rats. Baicalin as a new drug has good prospects in the treatment of SAP.

Effect of Octreotide on cell-cycle kinetics and serum CEA level in hepatic metastases of colonic adenocarcinoma

AIM To study the inhibitory effect of somatostatin analogue (Octreotide) in tumor growth. METHODS The influence of cell cycle kinetics on hepatic metastases of BALB/c mice colonic adenocarcinoma (CT26) with Octreotide treatment in vivo was investigated by flow cytometry. The serum CEA levels were also determined. RESULTS The results showed that the proliferative index (PI) and the S phase fraction in hepatic tumors of mice treated with Octreotide decreased markedly and the G 0/G 1 phase fraction increased significantly in comparison with the control ( P <0 01). After administration of Octreotide, the serum CEA level were also lower than that of control group. The incidence of liver metastases in the treated group were lower than that of control. The mice body weight loss was slow and the survival was long in the treated group. Furthermore, the changes of PI and the fraction distribution of S phase or G 0/G 1 phase in cell cycle were closely related to the serum CEA levels. CONCLUSION Octreotide may be useful for inhibiting the hepatic metastases of colonic carcinoma.