肝缺血再灌注损伤相关通路的研究进展

肝缺血再灌注损伤(hepatic ischemia reperfusion injure,HIRI)是在肝移植、肝切除等外科手术中的常见并发症,是引起肝损伤的一个重要原因,可能会导致肝功能衰竭等。目前HIRI相关信号通路与防治措施的实验性研究虽然较多,但临床疗效仍存在争议,因此HIRI的防治依然是巨大挑战。HIRI的相关信号通路作用机制不完全明确,且不断有新的信号通路被发现。笔者从损伤性作用、保护性作用、双向调节、相互串扰四个方面对将HIRI中的信号通路进行归纳阐述,为今后的临床治疗提供新思路。

Hepatoprotective effects of baicalein against CCl 4-induced acute liver injury in mice

AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in mice.METHODS:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 d.The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement.Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation.Serum interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain reaction.RESULTS:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice.The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the control.The expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 h.Furthermore,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver regeneration.CONCLUSION:Baicalein may be a therapeutic candidate for acute liver injury.Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.

Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats

AIM： To study the protective effect of Astragalus rnernbranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS： A total of 32 SD rats were randomly divided into four groups （n = 8, each group）： normal group, model group, low dosage group （treated with 10 g/kg Astragalus membranaceus） and high dosage group （treated with 20 g/kg Astragalus membranaceus）. The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution （3 mL） was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid （LD）, nitric oxide （NO）, endothelin-1 （ET-1）, malondialdehyde （MDA） and the activity of superoxide dismutase （SOD）, glutathione peroxidase （GSH-PX） in intestinal mucosa were determined. RESULTS： The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu＇s score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION： High dose Astraga/us membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.

Protective Effects of Oyster Extract Against Hepatic Tissue Injury in Alcoholic Liver Diseases

Oyster extract is an effective bioactivity component. It has abundant nutritional value and antiviral, antitumor and im- mune defense fimctions. The role of oyster extract in treating liver injury has been paid more attention. We use Wistar rats to make alcoholic liver disease model through injecting alcohol into rats＇ stomachs. These rats were randomly divided into five groups： model group, control group, low-dose, middle-dose and high-dose experimental group with a dose of 0.12gkg-1, 0.40gkg-1, and 1.20gkg-1 alcoholic. After nine weeks, serum biomarkers （ALT, AST, TG and TCHO）, malondialdehyde （MDA）, glutathione （GSH）, C3a, CSa, IL-17, TNF-a, anti-MAA-HAS IgC~ CD3＋, CD4＋, CDS＋, NK cell activation and zinc content were assessed. The results showed that the serum biomarkers（ALT, AST, TG and TCHO）, MDA content, anti-MAA-HSA IgG, serum C3a, CSa IL-17 and TNF-a levels of oyster extract treatment groups were significantly decreased in comparison with model group. On the contrary, GSH showed ad- verse trend. Serum CD3＋, CD4＋ and NK cell activation were significantly increased in middle-dose group and high-dose group compared with model group, and there was decrease of CD8＋ activity in high-dose group. Plasma Zn level was decreased in model group compared with that in control group. Meanwhile, Mean plasma Zn levels increased dramatically following the dose increase of a given oyster extract.

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxicischemic event.This devastating condition can lead to long-term neurological deficits or even death.After hypoxic-ischemic brain injury,a variety of specific cellular mechanisms are set in motion,triggering cell damage and finally producing cell death.Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury.After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury,various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.Among them,the endocannabinoid system emerges as a natural system of neuroprotection.The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury,acting as a natural neuroprotectant.The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury,and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

Attenuation law of explosive stress wave in damaged rock mass

The attenuation regularity of explosion stress waves in damaged rocks is discussed according to physical and geometric attenuation of waves in this paper. The relation between numerical decrement and damaged parameter is given and the results have an important significance to design and control blasting effect accurately in a concrete rock.

Study on the Uncertainty of Earthquake Damage Prediction Based on Damage Indices for RC Structures

Seismic damage indices of structure are widely used to quantificationally analyze structural damage levels under earthquake action. In this paper, a five-storey building model and a seventeen-storey building model are established. According to seven typical indices and different earthquake-inputs, a structural damage prediction is performed, with the results showing serious uncertainty of structural damage prediction due to different indices. Understanding of this phenomenon aids the comprehension and application of the results of earthquake damage prediction.

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury

Objective: To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI). Methods: An acute experimental closed TBI model in rats was induced by a fluid percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed. Results: After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P< 0.05 ). No significant difference between the saline treated group and the brain injury group (P> 0.05 ) was observed.Conclusions: Ganglioside GM1 does have obvious neuroprotective effect on early TBI.

Effect of glycyrrhizin on traumatic brain injury in rats and its mechanism

Objective： To investigate the neuropro- tective effects of glycyrrhizin （Gly） as well as its effect on expression of high-mobility group box 1 （HMGB1） in rats after traumatic brain injury （TBI）. Methods： Male Sprague-Dawley rats were randomly divided into three groups： sham group, TBI group, and TBI＋Gly group （n=36 per group）. Rat TBI model was made by using the modified Feeney＇s method. In TBI＋Gly group, Gly was administered intravenously at a dosage of l0 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB 1/HMGB 1 receptors including toll-like receptor 4 （TLR4） and receptor for advanced glycation end products （RAGE）/nuclear fac- tor-κ B（NF- κ B） signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB l, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed. Results： Beam walking performance impairment and brain edema were significantly reduced in TBI＋Gly group compared with TBI group; meanwhile, the over-expressions of HMGB 1PHMGB 1 receptors （TLR4 and RAGE）/NF- κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB 1, RAGE and TLR4- positive cells and apoptotic cells were respectively 58.37%±5.06%, 54.15%±4.65%, 65.50%± 4.83%, 52.02%±4.63% in TBI group and 39.99%±4.99%, 34.87%±5.02%, 43.33%±4.54%, 37.84%±5.16% in TBI＋Gly group （all P〈0.01 compared with TBI group）. Conclusion： Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regula- tion of HMGB 1/HMGB 1 receptors （TLR4 and RAGE）/NF- κB - mediated inflammatory responses in the injured rat brain.

Changes of arginine vasopressin in elderly patients with acute traumatic cerebral injury

Objective: To investigate the changes and clinical significance of arginine vasopressin (AVP) in elderly patients with acute traumatic cerebral injury. Methods: With radioimmunoassay, the plasma levels of AVP were measured in 32 elderly patients with acute traumatic cerebral injury, 30 traumatic patients without cerebral injury and 30 healthy elderly volunteers, respectively. Results: The plasma level of AVP in patients with acute traumatic cerebral injury in the early stage ( 48.30 ng/L±8.28 ng/L ) was much higher than that of the traumatic patients without cerebral injury ( 25.56 ng/L±4.64 ng/L , P< 0.01 ), which was much higher than that of the healthy volunteers ( 5.06 ng/L±4.12 ng/L , P< 0.01 ). The level of AVP in the patients with acute traumatic cerebral injury was negatively related with GCS scores. Conclusions: AVP may play an important role in the pathophysiological process in patients with acute traumatic cerebral injury in the early stage. The severer the cerebral injury is, the higher the level of AVP is, which indicates that the level of AVP may be one of the severity indices of traumatic cerebral injury in elderly patients.

Effect of methylprednisolone on reperfusion injury in severe uncontrolled hemorrhagic shock

Objective: To study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved. Methods: Twelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer’s (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T 1), when MAP decreased to 20 mm Hg (T 2), 60 min (T 3) and 120 min (T 4) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly. Results: Infusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P< 0.01 and P< 0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T 3 and T 4 decreased as compared with that at T 1 but a stepwise increase was present. At T 4, blood SOD level was significantly higher in Group II than in Group I (P< 0.01). At T 3 and T 4, MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T 4) was higher in Group II than in Group I (P< 0.05). Conclusions: MP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.