奥曲肽对肝动脉栓塞治疗大鼠肝癌影响的实验研究

目的　观察奥曲肽(octreotide)降低肝动脉栓塞(HAE)促进肿瘤新生血管生长的作用以及抑瘤作用。方法　采用大鼠肝内种植Walker 256瘤株制作肝癌模型,分为对照组、Octreotide组、HAE组和HAE+octreotide组共四组。定期切取肿瘤标本测量肿瘤体积,检测标本中的血管内皮生长因子(VEGF)的表达及微血管密度(MVD)。结果　各干预组肿瘤体积均小于对照组(P<0.01), HAE+octreotide组肿瘤体积也小于 HAE组(P<0.05); HAE+octrotide组 VEGF表达低于HAE组(P<0.05);Octreotide组、HAE+octreotide组 MVD表达低于对照组(P<0.05)。结论　在对大鼠肝癌的治疗中,行肝动脉栓塞时联用奥曲肽,可降低单纯肝动脉栓塞引起的癌组织 VEGF高表达,减少肿瘤新生血管形成,加强其抑瘤作用。     

The long-acting somatostatin analogue octreotide alleviates symptoms by reducing posttranslational conversion of prepro-glucagon to glucagon in a patient with malignant glucagonoma,but does not prevent tumor growth

A 52-year-old female with metastatic glucagonoma secreting glucagon and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 g/l (normal <0.2) and within 2 days 3 × 200 g octreotide daily suppressed plasma glucagon to 2.2–2.5 g/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal <0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very highdosesof octreotide (4 × 600 g/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processing of preproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.Abbreviations CGA chromogranin A - IRG immunoreactive glucagon - OC octreotide Correspondence to: D. Reinwein     

Distribution and pharmacological characterization of somatostatin receptor binding sites in the sheep brain

Somatostatin binding sites have been localized and quantified in the sheep brain using ¹²⁵I-Tyr₀-DTrp₈-somatostatin, by quantitative high resolution light microscopic autoradiography. Sections were analyzed by densitometry on radioautographic film, and subsequently on slides coated with photoemulsion. Specific somatostatin binding sites were concentrated in the medial habenula, superior colliculus, dorsal motor nucleus of the vagus nerve, inferior olive, spinal trigeminal nucleus, and cerebellum. In competition experiments, octreotide, a sst2/sst3/sst5 selective agonist only partially displaced ¹²⁵I-Tyr₀-DTrp₈-somatostatin in the three cerebellar layers while it was fully active as compared to somatostatin 14 and 28 in the deeper layers of the parietal cortex. Moderate to low somatostatin receptor densities were present in the mesencephalic periaqueductal gray, dorsal raphe, thalamic paraventricular nucleus, interpeduncular nucleus, pineal gland, dorsal tegmental, dorsolateral tegmental and parabrachial nuclei, nucleus of the solitary tract. The distribution of somatostatin binding sites generally correlates with the data obtained on slides dipped in photoemulsion which provided better resolution and more precise localization. In most of the labeled areas, ¹²⁵I-Tyr₀-DTrp₈-somatostatin receptor binding was distributed between both neuropil and perikarya. Perikarya bearing ¹²⁵I-Tyr₀-DTrp₈-somatostatin receptors were observed in areas which did not display detectable binding sites on film such as the preoptic-anterior hypothalamic complex and arcuate nucleus and in the locus coeruleus. In conclusion, the distribution of ¹²⁵I-Tyr₀-DTrp₈-somatostatin binding sites in sheep brain is very reminiscent of other mammals being closer to the human than to rodents.     

大承气汤联合清热通腑灌肠方治疗急性胰腺炎疗效研究

目的:观察大承气汤联合清热通腑灌肠方治疗急性胰腺炎的临床疗效。方法:将96例已经确诊为急性胰腺炎的患者采用简单随机法分为对照组(n=48)和观察组(n=48)。对照组给予奥曲肽治疗,而观察组在奥曲肽基础上给予大承气汤口服联合清热通腑灌肠方保留灌肠治疗。比较两组胰腺体部血流指标、中医证候积分、Balthazar CT重症度指数分级及血淀粉酶的差异,统计两组临床疗效。结果:两组患者治疗前中医证候积分、Balthazar CT重症度指数分级比较,差异无统计学意义(均P>0.05)。两组中医证候总积分、主证和次证积分在治疗后均下降,且观察组中医证候总积分低于对照组,差异有统计学意义(均P<0.05)。治疗后观察组Balthazar CT重症度指数分级中Ⅰ级占比增加,Ⅲ级占比减少。治疗前,两组患者胰腺体部血流指标、血淀粉酶比较,差异无统计学意义(均P>0.05)。治疗后,两组胰腺体部血流量(BF)、血容量(BV)均高于治疗前,血淀粉酶及胰腺体部毛细血管表面通透性(PS)均低于治疗前,差异有统计学意义(均P<0.05)。治疗后,观察组胰腺体部BF、BV高于对照组,胰腺体部P...     

急性坏死性胰腺炎大鼠胰生长抑素受体的变化与奥曲肽治疗的作用机制

目的研究急性坏死性胰腺炎（ANP）时胰生长抑素受体（SSTR）的表达、胰组织血流改变及其与二十碳烯酸代谢的关系,探讨生长抑素类似剂奥曲肽治疗ANP的作用机制。方法以牛磺胆酸钠胰胆管注射诱发大鼠ANP模型,作125I-生长抑素-14受体放射配基结合实验,原位杂交检测胰组织SSTR2mRNA表达,组织血流仪测量胰组织血流,放免法检测血浆二十碳烯酸代谢物等。结果正常大鼠胰SSTR水平为110±58fmol/mg膜蛋白;ANP发病后3、6、12h,胰SSTR显著减低,SSTR2mRNA原位杂交信号显著减弱,胰组织血流明显降低,血栓素B2显著增高;奥曲肽给药组胰组织血流降低和二十碳烯酸异常代谢显著矫正,病理损害减轻。结论急性坏死性胰腺炎时胰组织SSTR表达显著降低。因此,生长抑素类似剂治疗ANP的机制可能主要与矫正二十碳烯酸异常代谢、改善胰组织微循环等有关,而受体介导的抑酶作用则是次要的。     

5-氟尿嘧啶加奥曲肽对乳腺癌细胞凋亡的影响

目的 探讨５－氟尿嘧啶（５－ＦＵ）加奥曲肽（善得定）对乳腺癌细胞凋亡的影响。方法取手术切除的１６例乳腺癌标本,制备癌单细胞悬液。每例癌细胞均分成４组：５－ＦＵ组（加入５－ＦＵ１０μｇ／ｍｌ）、善得定组（加入善得定０．１μｇ／ｍｌ）、５－ＦＵ加善得定组（加入５－ＦＵ１０μｇ／ｍｌ、善和定０１μｇ／ｍｌ）及对照组（不加任何药物）。用ＤＮＡ断端标记法（ＴＤＴ法）检测乳腺癌细胞癌细胞凋亡率。结果 １６例标     

奥曲肽治疗大鼠急性坏死性胰腺炎并急性肺损伤的实验研究

目的探讨奥曲肽对急性坏死性胰腺炎并急性肺损伤治疗影响。方法选日龄21 dSD大鼠为实验对象,并随机分为实验组(E组,n=6)、治疗组(T组,n=6)和对照组(C组,n=6)。采用十二指肠结扎胰管注射5%牛磺胆酸钠法建立急性坏死性胰腺炎并发急性肺损伤动物模型。E组在胰管中注入5%牛磺胆酸钠,C组注入生理盐水,T组在注入5%牛磺胆酸钠前1 h静脉注入生长抑素类药物奥曲肽。0、2、4、6 h分别取动脉血作血气分析,取静脉血作淀粉酶测定,6 h后取右肺进行支气管肺泡灌洗,灌洗液做中性粒细胞计数、分类和白蛋白含量分析。然后取左肺做肺湿重和肺干重称重,计算两者比值。结果注射5%牛磺胆酸钠2 h后,E组动物PaO2升高,4 h开始下降,6 h下降更明显,C组各时段变化无显著性,而T组变化规律与E组相似,但变化幅度明显减小。血淀粉酶都表现出相似的特征。支气管肺泡灌洗液白蛋白、中性粒细胞计数和分类,E组与C、T比较有显著性差异,C组与T组比较无显著性差异。结论生长抑素类药物奥曲肽能明显降低急性坏死性胰腺炎并肺损伤大鼠的肺泡炎性渗出,从而减轻肺损伤。