Liver ; metabolism ; physiopathology ; Microdialysis ; methods

Alcohol Drinking ; adverse effects ; Fatty Liver ; metabolism ; physiopathology ; Fatty Liver, Alcoholic ; metabolism ; physiopathology ; Female ; Humans ; Male

Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
Apoptosis ; Ceramides ; metabolism ; Fatty Liver ; metabolism ; physiopathology ; Humans ; Liver Diseases ; metabolism ; physiopathology ; Lysophospholipids ; metabolism ; Reperfusion Injury ; metabolism ; physiopathology ; Sphingolipids ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

As the most abundant liver-specific microRNA, microRNA-122 (miR-122) is involved in various physiological processes in hepatic function as well as in liver pathology. There is now compelling evidence that miR-122, as a regulator of gene networks and pathways in hepatocytes, plays a central role in diverse aspects of hepatic function and in the progress of liver diseases. This liver-enriched transcription factors-regulated miRNA promotes differentiation of hepatocytes and regulates lipid metabolism. With regard to liver diseases, miR-122 was shown to stimulate hepatitis C virus (HCV) replication through a unique and unusual interaction with two binding sites in the 5'-UTR of HCV genome to mediate the stability of the viral RNA, whereas inhibit the expression and replication of hepatitis B virus (HBV) by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway. In addition, miR-122 acts as a suppressor of cell proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity. Notably, a clinical trial targeting miR-122 with the anti-miR-122 oligonucleotides miravirsen, the first miRNA targeted drug, has been initiated for treatment of HCV infection. With further understanding of the comprehensive roles of miR-122 in hepatic functions and the mechanisms involved in miR-122 down-regulation in chronic hepatitis or hepatocellular carcinoma, miR-122 appears to be a promising candidate for effective therapeutic approaches against tumor and infectious diseases.
Humans ; Lipid Metabolism ; genetics ; Liver ; growth & development ; metabolism ; physiopathology ; Liver Diseases ; genetics ; physiopathology ; MicroRNAs ; genetics ; metabolism ; Models, Biological

Blood Vessels ; chemistry ; physiopathology ; Carcinoma, Hepatocellular ; metabolism ; physiopathology ; Elasticity ; Humans ; Liver Neoplasms ; metabolism ; physiopathology ; Rupture, Spontaneous ; metabolism ; physiopathology ; von Willebrand Factor ; metabolism

To investigate the role of heme oxygenase(HO), a catalyzing enzyme of heme to produce CO, in modulation of systemic circulation in CCl4-induced cirrhotic rats. Saline(vehicle) and ZnPP were s.c. injected into the posterior necks of rats respectively and the rats were then anesthetized by pentobarbital sodium in four hours. Mean arterial pressure (MAP, kPa), heart rate (HR, b/min) and portal pressure (PP, cm/H2O) were measured by indwelling catheter. Plasma CO was determined by Chalmers method. Heme oxygenase acivity was determined by the rate of bilirubin formation. The cirrhotic rats showed significant hyperdynamic circulation indicated by decreased mean arterial pressure [MAP, (15.6+/-1.7) vs (18.9+/-0.9) kPa, t = 4.52, P less than 0.01] and increased portal pressure [PP, (16.7+/-0.8) vs (8.8+/-0.3) cm H2O, t = 23.10, P less than 0.01] as compared to normal control rats(NS). ZnPP could cause a significant increase in MAP [(17.3+/-1.5) vs (15.6+/-1.7) kPa, t = 2.18, P less than 0.05] and significant decrease in PP [(13.2+/-0.7) vs (16.7+/-0.8) cm H2O, t = 8.53, P less than 0.01] in cirrhotic rats. The cirrhotic group presented a significant increase in plasma CO [(18.0+/-1.9) vs (10.4+/-1.3)mumol/L, t = 8.42, P less than 0.01] and HO activity in the spleens [(11.1+/-0.9) vs (6.5+/-0.9) nmol bilirubin/mg protein/h, t = 9.28, P less than 0.01] and intestines [(2.5+/-0.1) vs. (1.3+/-0.2) nmol bilirubin/mg protein/h, t = 15.1, P less than 0.01]. ZnPP could cause significant decreases in plasma CO and HO activity in liver, spleen and intestine of both control and cirrhotic rats. HO-CO system activation may be an important reason for the hemodynamic disturbance of liver cirrhosis.
Animals ; Carbon Monoxide ; metabolism ; Heme Oxygenase (Decyclizing) ; metabolism ; Hemodynamics ; Liver ; physiopathology ; Liver Cirrhosis, Experimental ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the clinical effect of acupuncture combined with TDP for treatment of postmenopausal patients with deficiency of liver and kidney syndrome and to explore its mechanism.

METHODSOne hundred and twelve cases were randomly divided into an acupuncture group and a medication group, 56 cases in each group. The acupuncture group was treated with acupuncture combined with TDP, Shenshu (BL 23), Mingmen (GV 4) and Guanyuan (CV 4) were selected as main points; the medication group was treated with oral administration of Nylestriol and Oryzanol. The therapeutic effects were evaluated after treatment of 3 months in the two groups, and the changes of estrogen,bone mineral density and endometrium of patients were observed before and after treatment.

RESULTSThe total effective rate of 94.6% in acupuncture group was superior to 75.0% in medication group (P<0.01), the acupuncture group was better than the medication group in increasing bone mineral density and decreasing the endometrial thickness (P<0.05, P<0.01), the medication group was better than the acupuncture group in decreasing the levels of serum follicular stimulating hormone (FSH) and luteinizing hormone (LH) and increasing the estradiol (E2) level (all P<0.01).

CONCLUSIONThe clinical effect of acupuncture combined with TDP for treatment of postmenopausal patients with deficiency of liver and kidney syndrome is significant, and it can increase bone mineral density, decrease endometrial thickness and obviously regulate the estrogen level.

Acupuncture Therapy ; Bone and Bones ; metabolism ; Estrogens ; metabolism ; Female ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Middle Aged ; Osteoporosis, Postmenopausal ; metabolism ; physiopathology ; therapy

BACKGROUNDMultiple organ dysfunction syndrome in the elderly (MODSE) is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models.

METHODSTwenty-four-month old rats (elderly) received intravenous injection of lipopolysaccharide (LPS) to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats.

RESULTSAll rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats ((43.4 ± 8.4)%) than in young rats ((24.2 ± 3.0)%). LPS injection also enhanced tumor necrosis factor a (TNF-a) concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-a level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 (TLR4) expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung.

CONCLUSIONLung is the first and most seriously injured organ in rat model of MODSE and it may play an "initiating" role in the development of MODSE.

Aging ; physiology ; Animals ; Female ; Lipopolysaccharides ; toxicity ; Liver ; metabolism ; physiopathology ; Lung ; metabolism ; physiopathology ; Male ; Multiple Organ Failure ; chemically induced ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo explore the efficacy and effect mechanism of the combined therapy of acupuncture and tapping method in the treatment of obesity and hyperlipidemia of liver qi stagnation and spleen deficiency pattern in the patients.

METHODSOne hundred and four female patients were randomized into a combined therapy of acupuncture and tapping (combined therapy group) group method and an acupuncture group, 52 cases in each group. In the acupuncture group, acupuncture was applied to Qimen (LR 14), Taichong (LR 3), Zhangmen (LR 13), Taibai (SP 3), Zusanli (ST 36), Geshu (BL 17), Ganshu (BL 18), Pishu (BL 20), etc. In the combined therapy group, on the basis of acupuncture treatment, the tapping method with plum blossom needle was used at each acupoint. The treatment was given once every two days, continuously for 3 months in the two groups. The indices were observed, including the obesity indices, such as body mass, body mass index (BMI), body fat percentage (F%) and obesity degree (A); the blood lipid levels such as total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL); the fat-islet axie relevant indices such as fasting plasma glucose (FBS), fasting leptin (FLP), fasting insulin (FINS), insulin sensitive index (ISI), insulin resistance in- dex (Homa IR), insulin secretion index (Homa-β) and autonomic nerve function index (Y value) before and after treatment in the patients of two groups. The efficacy was compared between the two groups.

RESULTSThe total effective rates were 96.2% (50/52) and 84.6% (44/52) in the combined therapy group and the acupuncture group respectively, without significant difference in comparison (P > 0.05). Obesity indices, blood lipid indices, fat-islet axie relevant indices and autonomic nerve function indices were all improved after treatment as compared with those before treatment in the two groups (P < 0.01, P < 0.05), and the improvements in the combined therapy group were much more significant (P < 0.01, P < 0.05).

CONCLUSIONThe combined therapy of acupuncture and tapping method achieves the double effects of weight loss and lipid loss in the treatment of obesity combined with hyperlipidemia. The effect mechanism is possibly related to the positive regulations of blood glucose, lipid metabolism and fat-islet axie in the patients.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Blood Glucose ; metabolism ; Female ; Humans ; Hyperlipidemias ; metabolism ; physiopathology ; therapy ; Insulin ; metabolism ; Leptin ; metabolism ; Liver ; physiopathology ; Middle Aged ; Obesity ; metabolism ; physiopathology ; therapy ; Qi ; Spleen ; physiopathology ; Treatment Outcome ; Triglycerides ; metabolism ; Young Adult

Hypertension is a common and frequently-occurring disease, as well as one of main causes for disability and death. With the social and economic development and the changes in lifestyle, risk factors of hypertension have also undergone significant changes, and thus the pathogenesis evolutional rules of hypertension in traditional Chinese medicine have also changed correspondingly. According to findings, metabolic disorder is an important feature of modern hypertension, as well as a significant cause for hypertension. Complementary and alternative medicine (CAM) plays a significant role in treating hypertension, with traditional Chinese medicines as major therapy. Turbidity and resistance, and liver-yang hyperactivity are the crucial pathogenesis of hypertension with metabolic disorder. In conclusion, therapy eliminating turbidity and calming liver is used to treat hypertension, which is worth promoting in clinical practice.
Complementary Therapies ; Humans ; Hypertension ; metabolism ; therapy ; Liver ; metabolism ; physiopathology ; Medicine, Chinese Traditional