Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats

Obesity is associated with gut dysbiosis and metabolic endotoxin.Junshanyinzhen tea extract(JSTE)reduced fat accumulation and body weight in obese mice.However,the effects and mechanism of JSTE in preventing obesity were unclear.Therefore,we used different doses of JSTE(75,150 and 300 mg/(kg·day))to evaluate the effect on high-fat diet(HFD)-induced rats under 8 weeks of intervention.Here,our results showed that JSTE could significantly reduce body weight gain,blood lipid levels and fat accumulation,improve fatty damage in liver tissue(P<0.05).In addition,JSTE increased the expression of intestinal tight junction proteins(P<0.05),relieved metabolic endotoxemia(P<0.05)and chronic low-grade inflammation in HFD rats.Sequencing of fecal samples showed that JSTE could effectively reverse the microbial diversity and the ratio of Firmicutes to Bacteroidetes to normal levels in HFD-fed rats.Desulfovibrioceae and Erysipelotrichaceae,which are positively related to obesity,were decreased by JSTE intervention(P<0.05).while Bifidobacteriaceae,Bacteroidaceae,Akkermansia,and Clostridium,which are negatively related to obesity,were increased.Together,these results suggested that JSTE might effectively prevent obesity by modulating gut microbiota dysbiosis,intestinal barrier dysfunction,metabolic endotoxemia and chronic low-grade infl ammation in HFD-induced rats.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

热休克蛋白A12A对内毒素血症肝损伤的作用及机制研究

目的:研究热休克蛋白A12A(heat shock protein A12A,HSPA12A)对内毒素血症肝损伤的影响及机制。方法:(1)采用脓毒症小鼠肝组织RNA测序的公共数据库,以生物信息学手段分析Hspa12a和多种载脂蛋白的mRNA表达变化。(2)采用6~8周龄Hspa12a基因敲除(Hspa12a knockout,Hspa12a-/-)鼠和野生型(wild type,WT)鼠,腹腔注射脂多糖(lipopolysaccharide,LPS)5 mg/kg诱导内毒素血症,以生理盐水(normal saline,NS)注射小鼠为对照组,分为NS-WT组、NS-Hspa12a-/-组、LPS-WT组和LPS-Hspa12a-/-组;LPS作用6 h后,收集肝组织,HE染色观察肝脏组织病理变化;免疫印迹和RT-PCR分析其中HSPA12A、ApoA1、ApoB、ApoM表达水平;分离血清,测定肝功能标志物丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天冬氨酸氨基转移酶(aspartate aminotransferase,AST)水平以及高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)和低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平。(3)WT鼠原代肝细胞过表达Hspa12a后,使用LPS(500 ng/mL)作用于肝细胞模拟内毒素血症肝损伤模型,6 h后检测肝细胞培养上清的ALT和AST水平。(4)根据是否发生脓毒症肝损伤将患者分为脓毒症肝损伤组和对照组,比较两组患者ALT、AST、HDL-C和LDL-C的差异。结果:(1)生物信息学分析显示,脓毒症小鼠肝脏Hspa12a、Apoa1、Apob和Apom的m RNA表达下降。(2)与NS-WT组相比,LPS-WT组肝组织出现明显损伤(P<0.001)、炎症病灶数量增多(P<0.01)、血清ALT(P<0.05)和AST(P<0.01)升高,同时肝组织中HSPA12A表达显著下降(P<0.05);而与LPS-WT组相比,LPS-Hspa12a-/-组肝脏病理变化更严重(P<0.05)且血清ALT(P<0.01)和AST(P<0.05)水平升高,HDL-C和LDL-C水平下降(P<0.01),肝组织载脂蛋白(ApoA1、ApoB、ApoM)表达降低(P<0.05,P<0.01)。(3)体外实验中LPS作用使肝细胞培养上清中ALT和AST水平升高(P<0.001),而过表达Hspa12a能够减轻LPS作用引起的ALT和AST水平升高(P<0.01)。(4)临床数据显示,出现脓毒症肝损伤的患者血浆中ALT和AST水平相比对照组显著升高(P<0.001),HDL-C和LDL-C水平显著下降(P<0.001)。结论:内毒素血症导致肝脏HSPA12A表达下调,其介导了内毒素血症肝损伤的发生,过表达Hspa12a能够保护内毒素血症引起的肝损伤,该作用可能与维持肝脏载脂蛋白及脂蛋白稳态有关。

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.

Changes in intestinal mucosal immune barrier in rats with endotoxemia

AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.

Effect of combined therapy of Yinchenhao Chengqi decoction and endoscopic sphincterotomy for endotoxemia in acute cholangitis

AIM To evaluate the therapeutic mechanism of Yinchenhao Chengqi (YCHCQ) decoction (containing mainly Herba Artemisia capillaris) combined with endoscopic sphincterotomy (EST) for endotoxemia (ETM) in acute cholangitis.METHODS Twenty-one cases of acute cholangitis with ETM were divided randomly into two groups: group A, 10 patients treated with YCHCQ decoction combined with EST, group B, 11 patients treated with EST. The incidence rate of ETM, plasmic ET, serum superoxide dismutase (SOD) activity, malonyldialdehyde (MDA), complement C3 and C-reactive protein (CRP) were studied respectively.RESULTS The ET level of group A (35.92ng/L±8.30ng/L) was significantly reduced after 7 days of treatment (P＜0.05) in contrast to that of group B (47.8ng/L±11.62ng/L), so did the level of MDA and CRP. But the SOD activity and C3 level in group A increased significantly (P＜0.05).CONCLUSION YCHCQ decoction combined with EST had a beneficial effect for ETM in acute cholangitis.INTRODUCTIONEndotoxemia (ETM) is one of the most important physiopathologic causes of acute cholangitis and it is the trigger of cytokines and inflammatory factors. In recent studies it has been found that Yinchenhao Chengqi (YCHCQ) decoction has a beneficial effect on ETM in acute cholangitis. With the development of endoscopic surgery, endoscopic sphincterotomy (EST) has become an effective replacement for some operations in the treatment of acute cholangitis[1]. The effect of YCHCQ decoction combined with EST on ET, oxygen free radical and complement C3 was observed in order to find out its therapeutic mechanism.

Dynamic changes and mechanism of intestinal endotoxemia in partially hepatectomized rats

AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into three groups： normal control （NC） group, partially hepatectomized （PH） group and a sham-operated （SO） group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation （ 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h）. NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin （ET） and diamine oxidase （DAO） levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells （KCs） in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS： Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation （r = 0.757, P 〈 0.05） between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum （La） particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION： The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,

Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (F PV ), with intraportal saline plus administration of LA (F PV + LA ), with lipopolysaccharide (LPS) infusion (F PLPS ), and with LPS infusion plus administration of LA (F PLPS + LA ). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4 ) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal-endotoxemia but not fructoseinduced liver and pancreatic abnormalities in a rodent model for metabolic syndrome.

Association between endotoxemia and histological features of nonalcoholic fatty liver disease

AIMTo assess whether surrogate biomarkers of endotoxemia were correlated with the histological features of nonalcoholic fatty liver disease (NAFLD).METHODSOne hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide (LPS)-binding protein (LBP) and anti-endotoxin core immunoglobulin G (EndoCab IgG) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores.RESULTSSerum LBP concentration was significantly increased in nonalcoholic steatohepatitis (NASH) patients as compared with nonalcoholic fatty liver (NAFL) subjects and was correlated with steatosis (r = 0.38, P &#x0003c; 0.0001) and ballooning scores (r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum EndoCab IgG concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between EndoCab IgG and histological findings.CONCLUSIONLBP/EndoCab IgG were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.

Effect of Dexamethasone on Nitric Oxide Synthase and Caspase-3 Gene Expressions in Endotoxemia in Neonate Rat Brain

Objective To investigate the gene and protein expressions of three isoforms of nitric oxide synthase (NOS) and gene expression of Caspase-3, and effect of dexamethasone on them in neonatal rats with lipopolysaccharide (LPS)-induced endotoxemic brain damage. Methods Expressions of the three isoforms of NOS and caspase-3 mRNA in the brain were investigated by RT-PCR in postnatal 7-day wistar rats with acute endotoxemia by intraperitoneal administration of LPS. Regional distributions of NOSs were examined by immunohistochemical technique. Results nNOS and Caspase-3 mRNA were obviously detected. eNOS mRNA was faintly expressed, but iNOS mRNA was undetectable in the control rat brain. The expressions of NOS mRNA of three isoforms were weak 2 h after LPS (5 mg/mg) delivery, peaked at 6 h, and thereafter, reduced gradually up to 24 h. The expression intensity was in the order of nNOS> iNOS> eNOS. Widespread nNOS, scattered eNOS distribution and negative iNOS were identified in the control rat brain and all isoforms of NOS could be induced by LPS which reached the apex at 24 h in the order of nNOS> iNOS> eNOS as detected by immunostaining. Although Caspase-3 mRNA could be found in all groups, DNA fragmentation was only seen at 6 h and 24 h. The expressions of NOS and Caspase-3 mRNA were inhibited in the rat brain when dexamethasone was administrated. Conclusion LPS-induced NO production induces apoptosis of neurons through mechanism involving the Caspase-3 activation, which may play an important role in the pathogenesis of brain damage during endotoxemia, and neuro-protective effects of dexamethasone may be partially realized by inhibiting the expression of NOS mRNA.

Pathogenetic effects of platelet activating factor on enterogenic endotoxemia after burn

INTRODUCTION Previous clinical and experimental studies haveindicated that an early endotoxemia occurred after amajor burn.It is unlikely that burn wound sepsis isthe source of circulating endotoxin in less than 12hour after burn.Increasing evidence demonstratesthat the bacteria and endotoxin in thegastrointestinal tract can pass through the gutbarrier into blood circulation to form enterogenicendotoxemia following burn.However。

Effect of Efferent Vagus Nerve Excitation by Electrical Stimulation on Acute Liver Injury in Rabbits with Endotoxemia

Objective:To study the effect of electrical stimulation of efferent vagus nerve on the acute liver injury induced by endotoxemia in rabbits. Methods:Sixteen rabbits were randomly divided into stimulation group(Group A,n=8) and control group (Group B,n=8).They were subjected to bilateral cervical vagotomy and intravenously challenged by lipopolysaccharide (LPS) (E.coli 0111:B4,DIFCO,USA) at a dose of 100 μg/kg injected within 30 min.The distal end of the left vagus nerve trunk was placed across bipolar electrodes connected to a stimulation module and controlled by an acquisition system.Stimuli with constant voltage (10V,5Hz,5ms) were applied twice to the nerve for 10 min before and after the administration of LPS in Group A.At the time 30,60,120,180,240,300 min before and after infusion of LPS respectively in each animal,blood samples were taken for late measurement of the serum Alanine aminotransferase (ALT),Aspartate aminotransferase (AST),tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10).Immediately after the experiment was finished,autopsy was performed and liver samples were taken to pathologic study. Results:Compared with Group B,the electrical stimulation of efferent vagus nerve could significantly decrease the contents of ALT,AST and TNF-α,but increase the contents of IL-10,in serum of Group A.It could also alleviate inflammation of liver tissue after LPS attack. Conclusion:The results suggest that excitation of the efferent vagus nerve can inhibit the inflammation cascade in liver after LPS challenge.Thus,it might have a protective effect on acute liver damage caused by endotoxemia.

Changes of enzyme chemistry of liver tissue and their image analysis during endotoxemia after thermal injury in rats

The changes of endogenous peroxidase (PO) and acid phosphatase (ACP) of the liver in rats which were inflicted with 20% TBSA full thickness burns and injected with endotoxin (1 ug/g body weight) were observed quantitatively with cytochemistry and computerized image analysis. Positive reaction of PO was found in the Kupffer cells (KCs) only in which the PO activity was significantly increased in the early stage and then decreased. This suggests that these changes are possibly compensatory at first and then decompensatory reactions of KCs to endotoxin challenge. ACP activity, in contrast to PO, was mostly localized in liver parenchymatous cells especially in the periphery of capillary bile ducts. It is considered that the ACP activity can reflect the functional state of lysosomes of hepatocytes which are damaged in the early stage of burn injury complicated by endotoxemia

Effects of hemorrhagic shock on endotoxemia and its molecular mechanism

In order to investigate whether hemorrhgic shock (HS) can enhance an individual’s sensitivity to endotoxin and the mechanism of this sensitization if it occurs, the changes of arterial blood pressure, plasma level of lactate and β-glucuronidase (β-G) and mortality rate were observed in rabbits of HS, lipopolysaccharide (LPS) and HS＋LPS groups. In addition. the expression of CD14 was determined in peritoneal macrophages in mice with HS.It was found that after the Infusion of LPS in HS＋LPS group, arterial blood pressure was significantly decreased while plasma lactate and β-G increased. The changes of these 3 parameters in HS＋LPS group were significantlydifferent from those of HS or LPS group at all time points. All the rabbits in HS＋LPS group died and those of HSand LPS groups survived. The expression of CD14 elevated in the peritoneal macrophages of mice during HS andsubsequent resuscitation. It is concluded that HS can markedly increase an individual’s sensitivity to endotoxin.which might be due to the upregulation of CD14 expression after HS.

Anthropometric indices, lipid profile, and lipopolysaccharide-binding protein levels in metabolic endotoxemia: A case-control study in Calabar Metropolis, Nigeria

Objectives: To determine the anthropometric indices, lipopolysaccharide-binding proteins (LBP), and lipid profile in patients with metabolic endotoxemia. Methods: The study comprised of 47 patients with metabolic endotoxemia (the metabolic endotoxemia group) and 43 controls (the control group). Patients in the metabolic endotoxemia group were categorized further into three subgroups including the normal weight group (n=8), the overweight group (n=12) and the obese group (n=27). Height, weight, waist, and hip circumference were measured, and waist-hip ratio (WHR) and body mass index (BMI) were calculated. LBP was determined by ELISA and total cholesterol, triglycerides, high density lipoprotein by the respective enzymatic colorimetric methods. In addition, low density lipoprotein and very low density lipoprotein were determined by Friedewald's formula. Results: The mean waist circumference (WC), hip circumference (HC), BMI, total cholesterol, low density lipoprotein, and LBP of the metabolic endotoxemia group were significantly higher (P<0.05) than those of the control group. WHR, TG, high density lipoprotein and very low density lipoprotein of the metabolic endotoxemia group were not significantly different (P>0.05) from those of the control group. The mean WC, HC, WHR, and BMI of the obese group with metabolic endotoxemia were significantly higher (P<0.05) than those of the overweight group and the normal weight group with metabolic endotoxemia. Significant positive correlations were obtained between BMI and LBP (r=0.610, P=0.001), total cholesterol and LBP (r=0.385, P=0.007), TG and LBP (r=0.356, P=0.014) in patients with metabolic endotoxemia. Conclusions: Metabolic endotoxemia arising from increased circulating level of bacterial derive particles consequent to perturbation in the gut microbial community and the elevated ;serum level of LBP may precede the development of obesity, characterized by dyslipidemia, dysregulation of gut energy harvest, and metabolic energy imbalance.

Effects of cholecystokinin octapeptide receptor on lung injury in endotoxemia rats

Objective:To investigate the effects of CCK-8 receptor on lung injury in endotoxemia rats. Methods: Male SD rats were randomized into four groups (n=6): control group (LPS+CCK-8 group), CCK-1R antagonist group, CCK-2R antagonist group, DFSO+PF group. The rats were injected by LPS (5 mg.kg-1). CCK-8 (20 μg.kg-1) was administered 30 min after LPS injection. Either a specific CCK-1R antagonist or CCK-2R antagonist (0.5.kg-1) was injected before CCK-8 treatment (after LPS 20min). The tidal volume (TV) was collected by a multi-channel data physiological recorder. The lung injury was observed by light and electron microscopy. The concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were measured by ELISA kits.Rresults: Compared with control group, the TV were significantly lower and the lung injuries were more serious in CCK-2R antagonist group. As well as the concentrations of TNF-α、IL-1 and IL-6 in lung homogenates were higher.Conclusion: CCK-2 receptor plays a major role in the effect of CCK-8 on lung injury in ETM rats.

清肠祛浊汤治疗肝硬化肠源性内毒素血症的临床效果及机制探讨

目的探讨清肠祛浊汤治疗肝硬化肠源性内毒素血症的效果及潜在机制。方法102例肝硬化肠源性内毒素血症患者,根据随机数字表法分为观察组、对照组1和对照组2,每组34例。三组患者均接受21 d常规临床治疗,对照组2患者加用乳果糖治疗,观察组加用清肠祛浊汤结肠滴注治疗。比较三组患者治疗效果及治疗前后血浆内毒素(ET)、血清炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)]水平。结果观察组患者的治疗总有效率为94.12%,显著高于对照组1的61.76%、对照组2的73.53%,差异具有统计学意义(P<0.05)。治疗后,三组患者血浆内毒素水平均较本组治疗前显著下降,差异具有统计学意义(P<0.05);观察组患者血浆内毒素(0.18±0.06)EU/ml低于对照组1的(0.37±0.09)EU/ml、对照组2的(0.29±0.08)EU/ml,差异具有统计学意义(P<0.05)。治疗后,三组患者血清IL-1β、IL-6和TNF-α水平均较本组治疗前下降,差异具有统计学意义(P<0.05);观察组患者血清IL-1β、IL-6和TNF-α分别为(50.08±15.31)、(79.22±24.76)、(9.89±3.26)pg/ml,显著低于对照组1的(77.80±29.84)、(180.89±50.25)、(24.56±8.76)pg/ml和对照组2的(78.41±25.31)、(147.85±13.80)、(18.79±7.09)pg/ml,差异具有统计学意义(P<0.05)。结论清肠祛浊汤治疗肝硬化肠源性内毒素血症具有明显的临床效果,可以显著降低患者血浆内毒素和血清炎症因子水平,为疾病的治疗提供参考和理论依据。

解毒化瘀护肾方治疗慢加急性肝衰竭并发肝肾综合征的效果观察

目的探讨解毒化瘀护肾方治疗慢加急性肝衰竭(ACLF)并发肝肾综合征(HRS)的临床疗效以及对内毒素血症的影响。方法收集2020年3月—2022年6月在广西中医药大学第一附属医院诊治的96例ACLF并发HRS患者的临床资料,按随机数字表法分为对照组及观察组,每组48例。两组均给予西医综合治疗,对照组单给予去甲肾上腺素及白蛋白治疗,观察组予解毒化瘀护肾方联合去甲肾上腺素、白蛋白治疗,疗程均为2周。比较治疗前后两组患者血清内毒素水平、证候积分、24 h尿量、肾功能、肝功能、凝血功能以及临床疗效的差异。计量资料2组间比较采用成组t检验,组内治疗前后比较采用配对t检验;计数资料2组间比较采用χ^(2)检验。结果治疗2周后,观察组中医证候积分显著低于对照组(P<0.05);观察组内毒素水平、尿素、肌酐、胱抑素C、凝血酶原时间较对照组降低,差异均有统计学意义(P值均<0.05),观察组肾小球滤过率、24 h尿量、血清Alb、凝血酶原时间活动度较对照组升高,差异均有统计学意义(P值均<0.05);治疗2周后观察组总有效率(87.50%)高于对照组(66.67%),差异有统计学意义(P<0.05)。结论在西医综合治疗的基础上,解毒化瘀护肾方能降低ACLF并发HRS患者的血清内毒素水平,改善其肝肾功能、凝血功能及增加尿量,疗效优于单纯西医治疗。