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Objective@#To observe the effects of Na+ /H+ exchanger 1 (NHE1) inhibitor on intestinal injury of rats with burn sepsis, and to explore the possible mechanism preliminarily.@*Methods@#Ninety SD rats were divided into control group, pure sepsis group, and NHE1 inhibitor group according to the random number table, with 30 rats in each group. Full-thickness scald (hereinafter referred to as burn) model with 20% total body surface area were reproduced on the back of rats in pure sepsis and NHE1 inhibitor groups, and then 50 μL liquid of Pseudomonas aeruginosa ATCC 27853 (2×105 colony forming unit/mL) were injected into the center of wounds on the back. Rats in NHE1 inhibitor group were intraperitoneally injected with 0.1 mmol/L NHE1 inhibitor cariporide (0.4 mg/kg) rapidly after the successful establishment of burn sepsis model, while rats in pure sepsis group were injected with the same volume of normal saline. Except for not being made burn wounds nor receiving bacterination, rats in control group were treated the same as those in pure sepsis group. Rats with burn sepsis in each group were laparotomized and injected with 200 mL fluorescein isothiocyanate (FITC)-dextran in the concentration of 0.1 mol/L in terminal ileum at 12 hours post injury, and their left ventricular blood and terminal ileum were collected 30 minutes later. The serum content of FITC-dextran was detected with fluorescence spectrophotometer (n=10); the morphology of intestinal tissue was observed with HE staining (n=10); the content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in serum and intestinal tissue was determined with enzyme-linked immunosorbent assay (n=20); the activity of myeloperoxidase (MPO) in serum and intestinal tissue was detected with colorimetric method (n=20); the protein expression of nuclear factor-kappa B-p65 (NF-κB-p65) and phosphorylation levels of mitogen-activated protein kinase (MAPK) signal pathway related proteins p38MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase 1/2 (JNK1/2) were determined by Western blotting (n=4). The same samples of rats in control group were collected for related detection at the same time point as above. Data were processed with one-way analysis of variance and SNK test.@*Results@#(1) The serum content of FITC-dextran of rats in pure sepsis group was significantly higher than that in control group (P<0.01), while the serum content of FITC-dextran of rats in NHE1 inhibitor group was significantly lower than that in pure sepsis group (P<0.01). Compared with that in control group, infiltration of a large number of inflammatory cells, ulcer and necrosis of intestinal mucosa of rats in pure sepsis group were observed. The injury condition of intestine of rats in NHE1 inhibitor group was better than that in pure sepsis group. (2) The serum content of IL-6, TNF-α, and MPO of rats in pure sepsis group was (387±42) and (164.7±10.1) ng/mL, and (7.5±1.5) U/mL, respectively, significantly higher than that in control group [(75±17) and (13.1±6.5) ng/mL, and (2.3±0.7) U/mL, respectively, with P values below 0.01]. The serum content of IL-6, TNF-α, and MPO of rats in NHE1 inhibitor group was (176±37) and (64.9±9.3) ng/mL, and (5.9±0.8) U/mL, respectively, which was significantly lower than that in pure sepsis group (with P values below 0.01). (3) The content of IL-6, TNF-α, and MPO in intestinal tissue of rats in pure sepsis group was (190±13) and (172.8±29.7) ng/mL, and (8.7±1.5) U/mL, respectively, significantly higher than that in control group [respectively (20±3) and (11.9±2.3) ng/mL, and (2.9±0.3) U/mL, with P values below 0.01]. The content of IL-6, TNF-α, and MPO of intestinal tissue of rats in NHE1 inhibitor group was (35±6) and (45.2±6.1) ng/mL, and (5.3±0.6) U/mL, respectively, significantly lower than that in pure sepsis group (with P values below 0.01). (4) The protein expression of NF-κB-p65 and phosphorylation levels of p38MAPK and ERK1/2 in intestinal tissue of rats in pure sepsis group were significantly higher than those in control group (with P values below 0.01); the protein expression of NF-κB-p65 and the phosphorylation level of p38MAPK in intestinal tissue of rats in NHE1 inhibitor group were significantly lower than those in pure sepsis group (with P values below 0.01); phosphorylation levels of JNK1/2 in intestinal tissue of rats in the three groups were similar (with P values above 0.05).@*Conclusions@#The inhibition of NHE1 can significantly alleviate the intestinal injury, and the mechanisms may be attributed to the regulation of NF-κB and p38MAPK signal pathway, resulting in inhibition of the inflammatory response of intestinal tract.
ABSTRACT
This review summarizes the epidemiology, etiology, clinical manifestation, treatment, follow-up of neonatal lupus erythematosus with focus on new discoveries on the etiology of the disease in recent years including anti-SSA/Ro and anti-SSB/La antibodies, serotonin (5-hydroxytryptamine 4), apoptosis of cardiac cells, calcium channels, maternal micro-chimera, genetic variants, to improve clinician awareness of the disease.
ABSTRACT
BACKGROUND: It has been reported that bioactivity is found to be favored by the co-operative behavior of silanol (Si-OH)or Ti-OH etc. groups on the material surface and the involved calcium ions. To confirm the hypothesis that a new family of organic-inorganic hybrid materials, which incorporate gelatin chains covalently into Si-O-Ti network, is synthesized through sol-gel procedure.OBJECTIVE: To synthesize a hybrid of gelatin and CaO-SiO2-TiO2 system which is used for bone repairing, and observe its structure and bioactivity.DESIGN: Randomized control observation.SETTING; the laboratory, School of Material Science and Engineering, Shaanxi University of Science and Technology. MATERIALS: Gelatin (Sinopharm Chemical Reagent Co., Ltd), titanic acid isopropyl ester (Gu'an Hengye Fine Chemicals Co., Ltd), γ-glycidoxy propyl trimethoxy silane (Jingzhou Jianghan Fine Chemicals Co., Ltd), calcium nitrate (Tianjin Bodi Chemicals Co., Ltd)METHODS: The experiment was carried out in the laboratory, School of Materials Sciences and Engineering, Shaanxi University of Science and Technology between April and August in 2006. A new type of bioactive organic-inorganic hybrid was synthesized through sol-gel processing starting from gelatin, γ-(2,3-glycidoxypropyl)trimethoxysilane (GPSM),Tetraisopropyltitanate (TiPT) and calcium nitrate. ①Structure of the hybrid: The structures of the products were investigated with Fourier transformed infrared (FT-IR) diffusive reflection spectroscope, X-ray diffraction (XRD) instrument and scanning electron microscope (SEM) respectively.②Bioactivity: The products Ti15Ca0 and Ti15Ca20 were soaked in a stimulated body fluid (SBF) to evaluate the morphology of the surfaces by SEM and thin-film XRD. MAIN OUTCOME MEASURES: The structure and bioactivity of the hybrid.RESULTS: ①The hybrid was completely amorphous and its surface was almost homogenous, which implied the covalent bonding between the organic component and inorganic component. FT-IR spectra result verified the occurrence of Si-OH group and Si-O-Ti bond, as well as the addition of TiPT supplied Si-O-Ti bond. ②There were lots of apatite crystallines formed on the surface of hybrid Ti15Ca20 after soaked in SBF for 7 days, which confirmed their in vitro bioactivity. These apatite particles were similar to the bioglass and other bioactive materials in the patterns. CONCLUSION: A new type of organic-inorganic hybrid material, which incorporates gelatin chains covalently into Si-O-Ti network, is synthesized through sol-gel procedure. There are lots of apatite and brushite crystals formed on the surface of the product Ti15Ca2O after soaking in SBF for 7 days, which obviously proves the bioactivity of the hybrid.