腹腔镜术后中药治疗对盆腔炎性不孕患者肿瘤坏死因子-α、白细胞介素-6的影响

【目的】观察腹腔镜术后中药治疗对不同程度盆腔炎性不孕患者肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的影响。【方法】收集因盆腔炎性不孕行腹腔镜手术治疗的患者85例,采用分层随机方法分为4组:手术组(轻度)20例,手术+中药组(轻度)22例,手术组(中度)21例,手术+中药组(中度)22例。收集同期因单纯性卵巢囊肿行腹腔镜手术患者20例作为非炎症对照组。比较治疗前后各组患者临床症状、体征的改善情况,采用酶联免疫吸附法测定各组患者治疗前后血清TNF-α、IL-6水平。【结果】(1)治疗后除手术组(轻度)的症状积分与治疗前比较差异无统计学意义(P>0.05)外,其余3组均较治疗前显著下降(P<0.05)。治疗后各组的体征积分均较治疗前显著降低(P<0.05)。治疗后,症状积分、体征积分手术+中药组(中度)显著低于手术组(中度)(P<0.05);而手术+中药组(轻度)与手术组(轻度)比较,差异无统计学意义(P>0.05)。(2)治疗后,血清TNF-α水平除手术组(轻度)与治疗前比较差异无统计学意义(P>0.05)外,其他3治疗组较治疗前显著降低,差异均有统计学意义(P<0.05)。治疗后相同粘连程度的2组比较,手术+中药组(中度)的血清TNF-α水平显著低于手术组(中度),差异有统计学意义(P<0.01);而手术+中药组(轻度)与手术组(轻度)比较,差异无统计学意义(P>0.05)。治疗后与非炎症对照组比较,除手术+中药组(轻度)差异无统计学意义(P>0.05)外,其他3组的血清TNF-α水平仍显著高于非炎症对照组,差异均有统计学意义(P<0.05或P<0.01)。(3)治疗后,血清IL-6水平除手术组(中度)较治疗前有降低趋势,但差异无统计学意义(P>0.05)外,其他3治疗组均较治疗前显著降低,差异均有统计学意义(P<0.05或P<0.01)。治疗后相同粘连程度的2组比较,无论轻度还是中度,手术+中药组显著低于手术组,差异均有统计学意义(P<0.05或P<0.01)。治疗后与非炎症对照组比较,各治疗组的血清IL-6水平仍显著高于非炎症对照组,差异均有统计学意义(P<0.05或P<0.01)。【结论】中药联合腹腔镜手术是治疗盆腔炎性不孕的有效方法,能明显改善患者的临床症状及体征;可降低盆腔炎性不孕患者血清TNF-α、IL-6水平,抑制盆腔炎性不孕患者炎症因子的过度升高及所致的机体过度免疫应答,恢复输卵管功能,改善盆腔的病理状态。     

Skeletal unloading-induced insulin-like growth factor 1 (IGF-1) nonresponsiveness is not shared by platelet-derived growth factor: the selective role of integrins in IGF-1 signaling

Integrin receptors bind extracellular matrix proteins, and this link between the cell membrane and the surrounding matrix may translate skeletal loading to biologic activity in osteoprogenitor cells. The interaction between integrin and growth factor receptors allows for mechanically induced regulation of growth factor signaling. Skeletal unloading leads to decreased bone formation and osteoblast proliferation that can be explained in part by a failure of insulin-like growth factor 1 (IGF-1) to activate its signaling pathways in unloaded bone. The aim of this study is to determine whether unloading-induced resistance is specific for IGF-1 or common to other skeletal growth factors, and to examine the regulatory role of integrins in IGF-1 signaling. Bone marrow osteoprogenitor (BMOp) cells were isolated from control or hindlimb suspended rats. Unloaded BMOp cells treated with IGF-1 failed to respond with increased proliferation, receptor phosphorylation, or signaling activation in the setting of intact ligand binding, whereas the platelet-derived growth factor (PDGF) response was fully intact. Pretreatment of control BMOp cells with an integrin inhibitor, echistatin, failed to disrupt PDGF signaling but blocked IGF-1 signaling. Recovery of IGF-1 signaling in unloaded BMOp cells followed the recovery of marked reduction in integrin expression induced by skeletal unloading. Selective targeting of integrin subunits with siRNA oligonucleotides revealed that integrin β1 and β3 are required for normal IGF-1 receptor phosphorylation. We conclude that integrins, in particular integrin β3, are regulators of IGF-1, but not PDGF, signaling in osteoblasts, suggesting that PDGF could be considered for investigation in prevention and/or treatment of bone loss during immobilization and other forms of skeletal unloading.     

Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo

While the epidermal growth factor receptor (EGFR)–mediated signaling pathway has been shown to have vital roles in many developmental and pathologic processes, its functions in the development and homeostasis of the skeletal system has been poorly defined. To address its in vivo role, we constructed transgenic and pharmacologic mouse models and used peripheral quantitative computed tomography (pQCT), micro–computed tomography (µCT) and histomorphometry to analyze their trabecular and cortical bone phenotypes. We initially deleted the EGFR in preosteoblasts/osteoblasts using a Cre/loxP system (Col‐Cre Egfr^f/f), but no bone phenotype was observed because of incomplete deletion of the Egfr genomic locus. To further reduce the remaining osteoblastic EGFR activity, we introduced an EGFR dominant‐negative allele, Wa5, and generated Col‐Cre Egfr^Wa5/f mice. At 3 and 7 months of age, both male and female mice exhibited a remarkable decrease in tibial trabecular bone mass with abnormalities in trabecular number and thickness. Histologic analyses revealed decreases in osteoblast number and mineralization activity and an increase in osteoclast number. Significant increases in trabecular pattern factor and structural model index indicate that trabecular microarchitecture was altered. The femurs of these mice were shorter and smaller with reduced cortical area and periosteal perimeter. Moreover, colony‐forming unit–fibroblast (CFU‐F) assay indicates that these mice had fewer bone marrow mesenchymal stem cells and committed progenitors. Similarly, administration of an EGFR inhibitor into wild‐type mice caused a significant reduction in trabecular bone volume. In contrast, Egfr^Dsk5/+ mice with a constitutively active EGFR allele displayed increases in trabecular and cortical bone content. Taken together, these data demonstrate that the EGFR signaling pathway is an important bone regulator and that it primarily plays an anabolic role in bone metabolism. © 2011 American Society for Bone and Mineral Research.     

Adaptation of Esophageal Mucosa to Acid- and Pepsin-Induced Damage (Role of Nitric Oxide and Epidermal Growth Factor)

To study whether the esophageal mucosa was ableto elicit mucosal adaptation, we induced esophagealdamage by perfusing acidified pepsin in rabbits. Mucosaladaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline)for 60 min prior to acidified pepsin (strong irritant).Macroscopic and microscopic esophageal injury, cellproliferation, and mucosal barrier function(H⁺, K⁺, hemoglobin flux rates)were studied. Preexposure of the esophageal mucosa toacidified saline significantly decreased both themucosal damage and the mucosal barrier dysfunctioninduced by acidified pepsin. The development of this phenomenon wasnondependent on cell proliferation. Concomitanttreatment with either the nitric oxide synthaseinhibitor, N^G-nitro-L-arginine, or theperfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, aninhibitor of the tyrosine kinase activities ligated tothe intracytoplasmatic domain of the EGF receptor,during the preexposure period completely reversed the protection induced by acid. We conclude thatthe rabbit esophageal mucosa shows mucosal adaptation toacid and pepsin. The development of this phenomenon isfast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxideand EGF-receptor-mediated mechanisms.     

Development of a cultured dermal substitute composed of a spongy matrix of hyaluronic acid and atelo-collagen combined with fibroblasts: fundamental evaluation

We have developed an allogeneic cultured dermal substitute (CDS) by cultivating fibroblasts on a 2-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col). The HA sponge was designed to have a honeycomb structure with many holes (0.5 mm diameter) separated by a distance of 4 mm. Part of the Col sponge was able to penetrate into these holes, and the resulting anchoring structure allows binding of a HA spongy layer with a Col spongy layer. The preparation of the CDS consists of two steps: (i) attachment of cells to the Col surface of the hydrated 2-layered spongy matrix and (ii) proliferation of cells on this sponge immersed in culture medium. The aim of the present study was to assess properties of fresh and cryopreserved CDS. Fibroblasts seeded on the Col surface of the 2-layered spongy matrix attached, proliferated and released vascular endothelial growth factor (VEGF) and fibronectin. The amount of VEGF released from cryopreserved CDS after thawing slowly in an incubator at 37°C and re-cultivation for 1 week was about 300 pg/ml. After thawing quickly in a water bath at 37°C and re-cultivation for 1 week, the amount of VEGF released was about 600 pg/ml. These findings indicate that the cryopreserved CDS maintained its ability to release a significant amount of VEGF. Retention of the therapeutic properties of CDS after cryopreservation is important for clinical use.     

Functional improvement by electro-acupuncture after transient middle cerebral artery occlusion in rats

Abstract

Functional recovery by the application of electro-acupuncture (EA) on different acupoints was investigated using a transient middle cerebral artery occlusion (MCAO) model in rat. Acupoints were Baihui (D20) plus Renzhong (D26) (MCAO + D group), and Hanyan (G4), Xuanlu (G5), Xuanli (G6), plus Qubin (G7) (MCAP + G group). Animals with EA treatment showed significant functional improvements from 12 days after the reperfusion against those without EA treatment. Among EA treated groups, MCAO + G showed a more significant recovery than MCAO + D. Infarct volume revealed the significant reduction in the EA treated groups especially in MCAO + G at 30 days. Immunohistochemical study showed a remarkable induction of vascular endothelial growth factor (VEGF) in astrocytes of the peri-infarct area at 30 days, more in EA treated groups than in groups treated with MCAO alone. These results suggest that the acupoints applied in this study are effective for the functional recovery, and an enhanced expression of VEGF may play a certain role in recovery process after stroke.     

Expression of metallothionein-III and cell death in differentiated catecholaminergic neuronal cells

Abstract

Metallothionein (MT)-III, an isomer of metallothionein, is also known to be a growth inhibitory factor. MT-III has been reported to decrease the number of surviving neuronal cells in culture medium containing brain extract. Using differentiated catecholaminergic neuronal CATH.a cells treated with dibutyryl cyclic AMP, we examined MT-III expression and the effect of mouse forebrain extract on cell viability. Increase in MT-III expression was revealed in the differentiated cells. Moreover, treatment with mouse forebrain extract induced apoptotic cell death in differentiated CATH.a cells, accompanied by decreases in both MT-III and a neuronal differentiation marker, growth-associated protein-43, expression in surviving cells. These results imply that MT-III expression during the developmental period may be associated with the regulation of normal neural differentiation.     

Trophic effect of Olmesartan,a novel AT1R antagonist,on spinal motor neurons in vitro and in vivo

Abstract

Olmesartan is a novel compound which has been shown to exhibit various neuropharmacological effects. For the purpose of clarifying the effect of Olmesartan on spinal motor neurons, we studied the following tests. We studied the effect in vitro of Olmesartan on neurite outgrowth and choline acetyltransferase (ChAT) activity in primary explant cultures of ventral spinal cord (VSCC) of fetal rats. Olmesartan-treated VSCC, compared with control VSCC, had a significant neurite outgrowth and increased activity of ChAT. The effect was dose-related in neurite outgrowth. However, there was no relationship between activity of ChAT and given doses of Olmesartan. We examined in vivo the effect of Olmesartan on axotomized spinal motor neuron death in the rat spinal cord. After post-natal unilateral section of sciatic nerve, there was approximately a 50% survival of motor neurons in the fourth lumbar segment. In comparison with vehicle, intraperitoneal injection of Olmesartan for consecutive 14 days reduced spinal motor neuron death. There was no relationship between number of surviving neurons and doses of Olmesartan. These in vitro and in vivo studies showed that Olmesartan has a neurotrophic effect on spinal motor neurons. Our data suggest a potential therapeutic use of Olmesartan in treating diseases that involve degeneration and death of motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis. [Neurol Res 2002; 24: 468-472]     

Response of neural precursor cells in the brain of Parkinson's disease mouse model after LIF administration

Abstract

Objective: To access the response of endogenous neural precursor cells (NPCs) in the area of substantia nigra (SN) in the mouse model of Parkinson's disease (PD). To evaluate whether leukemia inhibitory factor (LIF) can up-regulate the expression of NPCs and their fate in differentiation.

Methods: NPCs were measured and the number and density were estimated using the confocal counting system in normal control (CON), normal control LIF treated (CON + LIF), PD (PD) and LIF treated PD (PD + LIF) mice.

Results: The PD + LIF group showed a statistically significant improvement in the number and density of NPCs compared with PD group, and NPCs are rarely seen in CON and CON + LIF groups.

Conclusion: LIF may be a useful treatment for PD by up-regulating the re-expression of NPCs, which may represent the neuroprotection mechanism of LIF.