胃旁路术对糖尿病大鼠的降糖作用及其机制

目的观察胃旁路术(GBP)对链脲佐菌素(STZ)诱发的糖尿病大鼠降糖作用。探讨其机制。方法SD大鼠注射STZ建立糖尿病模型后分为手术组(O组)、假手术组(S组)、饮食控制组(F组)、对照组(C组),每组8只,测术前,术后第1、2、3、4、8周空腹和口服葡萄糖后血糖、胰岛素、胰高血糖素样肽-1(GLP-1)和体重、平均进食量。结果O组GBP后3周,空腹和餐后血糖分别由(16.84±3.82)、(31.88±6.22)mmol/L下降到(13.24±3.53)、(17.35±3.47)mmol/L(P值均＜0.05),空腹和餐后胰岛素分别由(28.66±8.17)、(30.73±8.99)mIU/L上升到(46.48±10.41)、(51.14±11.45)mIU/L(P值均＜0.01)。空腹和餐后GLP-1分别由(7.02±2.10)、(42.20±11.16)pmol/L上升到(25.16±7.30)、(97.83±30.23)pmol/L(P值均＜0.01)。GLP-1和血糖成负相关(P＜0.01),GLP-1和胰岛素成正相关(P＜0.01)。S组体重改变与O组相似,血糖无明显下降；F组控制平均进食量约为O组的1/3并致显著体重下降,血糖下降没有O组明显(P＜0.05)。结论GBP能显著降低STZ大鼠血糖,可能通过术后GLP-1分泌增多起作用。GBP的降糖作用与术后大鼠饮食减少和体重下降无关。     

Influence of omentectomy on peritoneal defense mechanisms in an experimental model of intra-abdominal infection

BACKGROUND/AIM: The omentum has an important role as part of peritoneal defense mechanisms. The aim of this study is to show the bactericidal activity of peritoneal fluid and the role of the omentum as a peritoneal defense mechanism in experimental animals with intra-abdominal infections. METHODS: 40 male Spraque-Dawley rats weighing between 250 and 300 g were used in this study. The rats were randomly divided into four groups consisting of 10 animals. The operative procedures were done under sterile conditions. In group I sham laparotomy was done. In group II, the distal part of the cecum was ligated, and cecum perforation was performed. In group III, total omentectomy was performed after cecal ligation and perforation. In group IV only omentectomy was performed. Baseline and 2- and 4-hour peritoneal fluid samples were taken using a Pasteur pipette during laparotomy under anesthesia. Total peritoneal cells counts, bactericidal activity of peritoneal fluid, and types of phagocytic cells in the peritoneal fluid were assessed. RESULTS: As compared with baseline values, the total peritoneal cell counts were increased at the 2nd and 4th h in all groups (p < 0.05). A significant increase was observed after 4 h as compared with 2 h in sham laparotomy, cecal ligation+perforation+omentectomy, and omentectomy groups (p < 0.05). A significant increase in the cell counts after 2 h was found in the other groups when compared to the sham laparotomy group (p = 0.0001). After 4 h, there was a significant difference between the groups, but especially prominent in the cecum ligation+perforation+omentectomy group (p = 0.0001). Proliferating colony counts of Escherichia coli and Pseudomonas Aeruginosa decreased after 2 h, and there was no proliferation in the subsequent cultures. It was observed that the macrophage counts significantly increased after 2 and 4 h as compared with baseline in intragroup assessments (p = 0.0001). In the intergroup assessment, an increase was observed in the macrophage counts at baseline and after 2 and 4 h, and this was significant in the cecal ligation+perforation+omentectomy group (p = 0.0001). In the omentectomy group, a significant decrease was observed in the macrophage counts between the 2nd and 4th h (p = 0.0001). CONCLUSION: Removal of the omentum in the presence of intra-abdominal infections causes the peripherally derived macrophages to take over the defensive role of macrophages of peritoneal origin as a compensatory mechanism, thus the peritoneal bactericidal activity against E. COLI, the major pathogen in intra-abdominal infections, does not change after omentectomy.     

The effect of CO2 pneumoperitoneum on the growth of a solid colon carcinoma in rats

Background: In order to investigate the effect of carbon dioxide (CO₂) pneumoperitoneum on solid colon carcinomas, we used a colon anastomosis tumor model in 30 male syngeneic WAG rats, which were divided, at random into three groups. Methods: In all rats, 10⁶ CC531 S colon carcinoma cells were injected as an enema into the colon. Subsequently, a transection and a reanastomosis of the colon descendens was performed via laparotomy. After 2 weeks, group 1 (n= 10) was anesthetized as an anesthesia control group. Group 2 (n= 10) had a laparotomy that was closed after 20 min. In group 3 (n= 10), a CO₂ pneumoperitoneum of ≤6 mmHg was created and maintained during 20 min. After 2 weeks, all rats were killed, and total tumor weight and volume was measured. Results: At necroscopy tumor growth was found in 16 rats (group 1: six; group 2: five; group 3: five). No difference in tumor growth (weight or volume) was found between the three groups. Conclusion: In our solid colon carcinoma model, CO₂ pneumoperitoneum did not enhance tumor growth.     

The defense mechanisms of the esophagus

Gastroesophageal reflux is a normal event, and the gastrointestinal tract possesses mechanisms to deal with the refluxed content so that symptoms are not produced. When the amount of refluxed material increases, or the quality changes, or one or more of the defense mechanisms breaks down, then the consequences occur in the esophagus. The variability of symptoms, of mucosal changes, and of motility patterns in response to pathologic gastroesophageal reflux imposes difficulties when one is trying to assess this disorder objectively.     

The kinetics of peritoneal clearance of Escherichia coli and Bacteroides fragilis and participating defense mechanisms

In a study using pigs, we delineated the dynamic character and the interplay of defense mechanisms that operate in the peritoneal cavity and their effectiveness against Escherichia coli and Bacteroides fragilis. The bacteria were extensively cleared during the first three hours. The concentration of both organisms in the peritoneal fluid decreased by up to 300,000-fold, and the final concentration was a function of the inoculum given. Clearance efficiency did not differ between a bolus dose and prolonged bacterial administration. Peritoneal absorption was a major eliminating mechanism during the first three hours but was limited to bacterial concentrations exceeding approximately 10(9) colony-forming units per milliliter of peritoneal fluid. Intraperitoneal elimination started immediately and continued for approximately six hours. Thereafter, residual bacteria were not eliminated, even though the defense capacity was intact. Prolonged bacterial administration, however, protracted the period for active bacterial destruction.     

The physiologic effect of the pneumoperitoneum on radiofrequency ablation

Background: Radiofrequency ablation (RFA) is gaining widespread acceptance as a safe and effective method for liver tumor ablation. Complete tumor ablation is essential for the success of the procedure. Multiple modalities have been explored in an effort to increase the size of the lesion created by RFA. The purpose of this study was to determine the physiologic effects of the pneumoperitoneum on RFA lesion size. Methods: A total of 32 RFA lesions were created in eight pigs. After the induction of anesthesia, pneumoperitoneums of 2, 12, and 24 mmHg were established sequentially in each animal. After an equilibration period of 2 min, RF was administered with a constant saline-infused (0.9%) needle at 25 W for 3 min. In subsequent and complementary experiments, both before and during RF administration at each intraperitoneal pressure (IPP), Doppler flow was measured by laparoscopic ultrasound in the portal vein and hepatic artery while blood pressure was monitored by a femoral arterial line. The animals were then killed humanely and the livers were harvested. Measurements were taken in three dimensions of the ablated areas, and the volume was calculated. Statistical analyses were performed using analysis of variance (ANOVA) and repeated measures test. Results: The average volumes of the lesions (in cm³) were 3.1 ± 1.8, 5.2 ± 1.7, and 6.7 ± 3.3 for IPP of 2, 12 and 24 mmHg, respectively; there was a significant difference between the area of lesion at an IPP of 2 mmHg and an IPP of 24 mmHg (p < 0.05). Blood flow in the portal vein also decreased significantly from 1.8 ± 0.6, 0.98 ± 0.5, and 0.43 ± 0.2 at IPP of 2, 12, and 24 mmHg, respectively (p < 0.001). Hepatic artery blood flow and peripheral blood pressure did not change significantly in the respective IPP groups. Conclusions: This study indicates that the volume of liver ablated by RF can be increased by augmenting the IPP. Our data support the theory that a decrease in portal blood flow results in decreased heat dissipation during RFA. The laparoscopic approach to RFA offers the advantage of allowing control of the IPP, which may result in a larger volume of ablated tissue per treatment than can be achieved with the percutaneous technique. These preliminary data on normal hepatic tissue must be confirmed clinically in the setting of hepatic tumors.     

Starvation-related alterations in free radical tissue defense mechanisms in rats

Alterations in endogenous free radical-scavenging defense mechanisms of rat tissues after body weight loss (induced by starvation for 72 h) associated with hypoinsulinemia were investigated. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione (GSSG) reductase as well as levels of reduced glutathione (GSH) were examined in several tissues and in erythrocytes. A complex pattern of changes was observed. CAT activities were increased in the heart and pancreas and decreased in the liver. SOD levels were decreased in the heart and increased in the kidney and pancreas. GSH-PX activities were increased only in the kidney, and levels of GSH were decreased only in the liver of starved animals. Erythrocytes from starved animals showed no alterations in the levels of major free radical-scavenging enzymes. However, GSSG reductase levels were lower in erythrocytes from starved animals, and this was associated with an increased susceptibility to H2O2-induced GSH depletion. Paradoxically, H2O2-induced malondialdehyde (MDA) production in erythrocytes from starved animals was lower than that in control erythrocytes. Our results suggest that, in studies of experimental diabetes, attention must be given to the influence of body weight loss per se on the biochemical alterations associated with this disease.     

还原型谷胱甘肽在预防糖尿病大鼠勃起功能障碍中的研究

目的探讨还原型谷胱甘肽(GSH)在预防糖尿病大鼠勃起功能障碍中的作用。方法通过腹腔注射链脲佐菌素65mg/kg建立糖尿病大鼠模型,然后随机分成DM组和DM+GSH组,DM+GSH组每天肌肉注射GSH200mg/kg。10周后观察大鼠勃起功能,并获取海绵体组织检测其谷胱甘肽、一氧化氮合酶(NOS)与丙二醛(MDA)水平,用TUNEL法检测细胞凋亡。结果成功建立糖尿病大鼠模型。与未注射GSH的DM组相比,DM+GSH组和正常对照组(C组)勃起功能更好,勃起率分别是20%,62.5%和100%。GSH水平DM+GSH组和C组明显比DM组高,其3组含量每克蛋白分别是(75.83±15.62)、(61.47±8.65)和(35.03±12.29)mg(P<0.05);NOS水平在DM+GSH组每毫克蛋白为(133.9±31.9)U,与正常对照组每毫克蛋白为(142.2±31.2)U相当,但较DM组每毫克蛋白为(58.4±18.9)U高(P<0.05);MDA含量在DM组每毫克蛋白为(3.71±0.62)nmol,明显高于正常对照组和DM+GSH组(P<0.05),这两组每毫克蛋白为(2.08±0.34)nmol和(2.44±0.28)nmol;细胞凋亡率在DM组、DM+GSH组和C组的分别是(22.6±3.6)%、(10.8±1.7)%和(7.2±2.1)%(P<0.05)。结论还原型谷胱甘肽对糖尿病大鼠阴茎组织有较好的抗氧化作用,能减少细胞凋亡,对延缓糖尿病性ED的发生有一定的作用。     

The effect of aminoguanidine on the blood-retinal barrier in streptozocin-induced diabetic rats.

The effect of aminoguanidine hydrochloride (AG) on the blood-retinal barrier was studied in rats with streptozocin-induced diabetes. Half of the rats were given AG (100 mg/kg/day) while the remainder received no treatment. Vitreous fluorophotometry was performed on all rats before STZ injection and 2 weeks after induction of diabetes mellitus. Two weeks after STZ injection the mean 60-minute vitreous fluorescein concentration following dye injection had increased more in the nontreated group than in the AG-treated group, suggesting that AG may have some beneficial effect on the breakdown of the blood-retinal barrier.     

The effect of timing of pneumoperitoneum on the inflammatory response

Background We examined the effects of an identical period of pneumoperitoneum applied at three different time points after lipopolysaccharide (LPS) challenge. Two different insufflation gases were also compared. Methods Male rats (n = 70) were injected intravenously with 1 mg/kg of LPS (time 0). The time relationship between a 1.5-h period of insufflation and initial LPS stimulation was the experimental variable. All rats were killed 6 h after injection. CO₂ and helium insufflation were investigated. Ten control rats received LPS only. Serum interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assay (ELISA). Hepatic expression of α₂-macroglobulin, β-fibrinogen, and metallothionein were measured by Northern blot analysis. Statistical analysis was performed using one-way analysis of variance (ANOVA). Results Expression of α₂-macroglobulin mRNA was lower in CO₂ groups compared to the control group (p < 0.05 at time 120 and 270). β-Fibrinogen message was diminished in CO₂ 0 and 120 groups compared to control. Serum levels of IL-6 and expression of metallothionein mRNA did not show significant differences between groups. Conclusions These findings suggest that CO₂ pneumoperitoneum downregulates the inflammatory response to LPS challenge. Start time of CO₂ insufflation does not appear to alter hepatic expression of acute phase genes. The mechanism of α₂-macroglobulin downregulation does not appear to be due to IL-6.     

Hemodynamic events in the peritoneal environment during pneumoperitoneum in dogs

Summary The purpose of this experimental study was to determine the hemodynamic conditions of intraperitoneal viscera during pneumoperitoneum by using either CO₂ gas or helium (He) for insufflation.In 16 mongrel dogs (divided into a CO₂ group and an He group) subjected to 14 mmHg pneumoperitoneum for 60 min, the following parameters were assessed at times before and 1, 2, 5, 15, 30, 45, and 60 min thereafter: (1) intestinal mucosal blood flow, by means of a laser-Doppler probe inplanted into a jejunal loop; (2) portal pressure and portal blood pCO₂, through a catheter inserted via a mesenteric jejunal vein; (3) intramural jejunal pH (pHi), by means of a Tonometer, which expresses the degree of tissue ischemia; (4) inferior vena cava pressure and blood pCO₂, through a catheter inserted via a femoral vein; and (5) from the systemic circulation pulse rate, arterial blood pressure, CO, CVP, PVP, SaO₂, pCO₂, and p_aO₂ were measured through a catheter placed into a femoral artery and a Swan-Ganz thermodilution catheter inserted via the external jugular vein: CI and SVR were then calculated.Jejunal mucosal blood flow was found decreased (P<0.0001) and pHi revealed gut mucosal ischemia. Portal and inferior vena cava pressures were found to be elevated (P<0.0001), as was blood pCO₂ of these vessels (P<0.001), in only the CO₂ group. From the systemic circulation, arterial blood pressure, CO, CI, SaO₂, and p_aO₂ revealed a decrease (P<0.001) while arterial pCO₂ (only CO₂ group), CVP, SVR, and PVP revealed an increase (P<0.001).We conclude that severe hemodynamic alterations, not only to the systemic circulation but mainly to the viscera of the peritoneal cavity, are prominent after pneumoperitoneum for laparoscopic surgery. Elevation of portal and inferior vena cava pressures leads to splanchnic blood flow congestion and ischemia, while the use of CO₂ seems to directly influence the pCO₂.     

The influence of a pneumoperitoneum on the peritoneal implantation of free intraperitoneal colon cancer cells

Background: In order to test the influence of a pneumoperitoneum on the peritoneal implantation of free intraperitoneal colon cancer cells, 40 male syngeneic WAG rats were at random divided into four groups. Methods: Group 1 (n=10) animals underwent a midline laparotomy and 10⁴ CC531 colon cancer cells were injected intraperitoneally (IP); in group 2 (n=10) 10⁴ CC531 cells were injected IP without further manipulation; in group 3 (n=10) a pneumoperitoneum up to 10 mmHg was created after the IP injection of the same amount of CC531 cells. The pneumoperitoneum was maintained for 15 min. Finally in group 4 (n=10) after the IP injection of 10⁴ CC531 cells and after the creation of a pneumoperitoneum, two 14-G IV catheters simulating trocars were introduced in each flank. A follow-up period of 8 weeks was used. Tumor implantation was scored according to the peritoneal cancer index of Eggermont and the index of Chauffert. Results: Tumor nodules were found varying from 60% in groups 1–3 to 50% in group 4. There was no statistical difference between the implantation rate in the four groups. A port-site recurrence was seen in group 4; all the other tumor implants were located in the mesenterium, omentum, internal genitals, or parietal peritoneum. Conclusions: The presence of a pneumoperitoneum does not enhance the implantation of free intraperitoneal malignant colon cancer cells in the rat, but the presence of a port may lead to abdominal-wall metastases.     

苯那普利、氯沙坦对糖尿病肾病大鼠Nephrin表达的影响

目的 探讨苯那普利、氯沙坦对糖尿病肾病大鼠Nephrin蛋白表达的影响。方法 建立糖尿病大鼠模型,分别使用苯那普利、氯沙坦治疗及联合治疗4、8周后,取出肾脏,采用逆转录聚合酶链式反应（RTPCR）检测肾皮质Nephrin mRNA的表达。结果 与对照组相比,糖尿病组Nephrin mRNA表达下调,苯那普利、氯沙坦治疗组较糖尿病组表达增加,两者联合治疗后增加更为明显。结论 苯那普利和氯沙坦联合应用,可以完全阻断血管紧张素Ⅱ（AngⅡ）,从而使Nephrin mRNA表达上调;肾小球足细胞损伤明显减轻、蛋白尿明显减少。     

The effect of intraperitoneal catalase on prevention of peritoneal adhesion formation in rats.

The objective of our study was to investigate the efficacy of catalase in preventing the formation of peritoneal adhesions induced by cecal serosal laceration in rats. A research study was set up using a randomized complete block design. This study was performed in the Experimental Surgical Research Center, Kahramanmaras Sutcuimam University, Kahramanmaras, Turkey. Thirty Wistar albino rats were assigned to 3 groups of 10 animals each. The animals were anesthetized, a median laparotomy was performed, and the cecum was traumatized. In the final stages of surgery, the first group received 30,000 U of catalase intraperitoneally (ip) (catalase group), the second group received 2 mL of saline solution ip (isotonic group), and the last group received no treatment (control group). All rats were sacrificed on day 14. Adhesions were counted and blood samples were taken for measuring the catalase level. There were significant differences between the adhesion scores among all groups (p < .05, Kruskal-Wallis test). The catalase group had significantly lower adhesion scores than the other groups (post hoc Mann-Whitney test). At day 14, blood catalase levels in the catalase group were significantly lower than in the other groups (p < .05). We conclude that introduction of catalase into the peritoneal cavity during surgery inhibited adhesion formation.     

黄腐酸钠对实验性糖尿病大鼠肾脏的保护作用

目的研究黄腐酸钠对糖尿病大鼠肾脏病变的保护作用及其机制。方法观察黄腐酸钠对肾小球形态，肾小球基底膜超微结构，尿白蛋白排出率的影响及血浆组织型纤溶酶原激活剂（ｔＰＡ）、纤溶酶原激活剂抑制物（ＰＡＩ１）活性改变。结果糖尿病大鼠血浆ｔＰＡ活性明显降低，而ＰＡＩ１活性升高。黄腐酸钠明显降低糖尿病大鼠尿白蛋白，抑制肾小球肥大，延缓肾小球基底膜增厚及足突融合，显著提高血浆ｔＰＡ活性而降低ＰＡＩ１活性。结论黄腐酸钠对糖尿病肾病具有保护作用。此作用可能与提高血浆纤溶活性有关。     

The effect of pneumoperitoneum in the steep Trendelenburg position on cerebral oxygenation

Background: daVinci^® robot‐assisted laparoscopic radical prostatectomy (RALP) requires pneumoperitoneum in the steep Trendelenburg position, which results in increased intracranial pressure and cerebral blood flow. The aim of this study was to evaluate the effect of pneumoperitoneum in a 30° Trendelenburg position on cerebral oxygenation using regional cerebral oxygen saturation (rSO₂). Methods: Thirty‐two male patients of ASA I and II physical status without previous episodes of cerebral ischemia or hemorrhage undergoing daVinci^® RALP were enrolled. The rSO₂ was continuously monitored with near‐infrared spectroscopy (INVOS^® 5100^?) during the study period. Measurements were obtained immediately after anesthesia induction (T0; baseline), 5 min after a 30° Trendelenburg position (T1), 5 min after 15 mmHg pneumoperitoneum in a supine position (T2), 30, 60 and 120 min after the pneumoperitoneum in a Trendelenburg position (T3, T4 and T5, respectively) and after desufflation in a supine position (T6). Results: The change in the left and right rSO₂ was statistically significant (Left P=0.004 and Right P=0.023). Both the right and the left rSO₂ increased significantly during pneumoperitoneum in a Trendelenburg position (from T3 to T5) and at T6 compared with the baseline value at T0. The partial pressure of carbon dioxide (PaCO₂) was increased significantly at T2, T3, T5 and T6 compared with the baseline value at T0. Conclusions: During daVinci^® RALP, cerebral oxygenation, as assessed by rSO₂, increased slightly, which suggests that the procedure did not induce cerebral ischemia. The PaCO₂ should be maintained within the normal limit during pneumoperitoneum in a Trendelenburg position in patients undergoing daVinci^® RALP because the rSO₂ increased in conjunctions with the increase in PaCO₂.     

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.