Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Effect of Nature and Flavor Subdivision of Ephedrae Herba on Rats Model of Harmful Fluid Retention in Upper Jiao / 中国实验方剂学杂志

Objective: To study the effective substance foundation of Ephedrae Herba and explore its mechanism, in order to further enrich the theory of drug resistance of Ephedrae Herba.Method: In this experiment, a compound model was used to establish rat model of Harmful Fluid Retention in upper Jiao. The Rats were randomly divided into model group, captopril group (4.38 mg·kg-1), Ephedrae Herba decoction group(468 mg·kg-1), polysaccharide group (265.36 mg·kg-1), volatile oil group (2.34 mg·kg-1), alkaloid group(40.71 mg·kg-1) and phenolic acid group (210.60 mg·kg-1), and normal group (10 mL·kg-1). The normal group and the model group were given the same volume of normal saline for four weeks. The 24 h urine volume of rats was collected by metabolic cage method. The changes of heart and lung tissue morphology were observed under light microscope. The heart index, lung index, left ventricular ejection fraction(LVEF), left ventricular short axis shortening rate(LVFS) and pulmonary permeability index, number(LPI), lung dry-wet ratio(W/D), creatine kinase isoenzyme(CK-MB), angiotensin Ⅱ(Ang Ⅱ), aldosterone(ALD), cardiac aquaporin 1(AQP1), lung AQP1, aquaporin-3(AQP3) and kidney AQP1, aquaporin-2(AQP2), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) change were detected.Result: Compared with the normal group, heart and lungs of the model group were significantly damaged. The amount of 24 h urine, LVEF, LVFS of model rats were significantly reduced(Pα were significantly increased(PPα were significantly increased (PPα were significantly reduced (PPConclusion: Alkaloid components "Wen" and "Xin" are the effective substance basis of its action. The mechanism may be related to the inhibition of renin angiotensin aldosterone system (RAAS) and the anti-inflammatory effect.

RAAS antagonist therapy for prevention of atrial fibrillation in hypertension / 中华全科医师杂志

Hypertension is the most common and controlable risk factor of atrial fibrillation (AF).Resin-angiotensin-aldosterone system (RAAS) antagonist therapy may reduce atrial remodeling and hold promise as “upstream” therapy for AF,especially for the patients with left ventricular hypertrophy and left ventricular dysfunction.The RAAS antagonist therapy for prevention of AF in hypertensive patients needs to be further explored in large scale randomized studies.

Comparative study on expelling water retention with drastic purgative of crude and vinegar stir-baked Kansui Radix in cancerous ascites rats / 中草药

Objective: To compare the function of expelling water retention with drastic purgative of crude and vinegar stir-baked Kansui Radix in cancerous ascites model rats. Methods: Furosemide was taken as positive control drug, and the cancerous ascites model rats were respectively orally administered with powder of crude and vinegar stir-baked Kansui Radix and their alcohol and water extract for 7 d. The amounts of urine and ascites, the levels of urinary sodium, potassium, chlorideion, and pH value, and the contents of PRA, Ang II, ALD, and ADH in serum were investigated. Results: Compared with model group, the amount of urine of each medication administration group significantly increased (P < 0.05, 0.01), the amount of ascites, the levels of urinary sodium, potassium, chlorideion, and pH value (P < 0.01), and the contents of PRA, Ang II, ALD, and ADH in serum all showed a significant decrease (P < 0.05, 0.01). Among them, the groups which were administered with powder of crude and vinegar stir-baked Kansui Radix were the most significant, and there was no significant difference between the two groups. Conclusion: The powders of crude and vinegar stir-baked Kansui Radix have a remarkable effect on expelling water retention with drastic purgative, and they could improve the symptom of cancerous ascites model rats.

Obesity Associated Hypertension: New Insights into Mechanism

With excess nutrition, the burden of obesity is a growing problem worldwide. The imbalance between energy intake and expenditure leads to variable disorders as all major risk factors for cardiovascular disease. There are many hypothetical mechanisms to explain obesity-associated hypertension. Activation of the RAAS is a key contributing factor in obesity. Particularly, the RAAS in adipose tissue plays a crucial role in adipose tissue dysfunction and obesity-induced inflammation. The phenotypic changes of adipocytes occur into hypertrophy and an inflammatory response in an autocrine and paracrine manner to impair adipocyte function, including insulin signaling pathway. Adipose tissue produce and secretes several molecules such as leptin, resistin, adiponectin, and visfatin, as well as cytokines such as TNF-alpha, IL-6, MCP-1, and IL-1. These adipokines are stimulated via the intracellular signaling pathways that regulate inflammation of adipose tissue. Inflammation and oxidative stress in adipose tissue are important to interact with the microvascular endothelium in the mechanisms of obesity-associated hypertension. Increased microvascular resistance raises blood pressure. Therefore, a regulatory link between microvascular and perivascular adipose tissue inflammation and adipokine synthesis are provided to explain the mechanism of obesity-associated hypertension.

The Effects of Aldosterone and Cytokines IL-1beta, TNF-alpha on the Expression of Angiotensin Converting Enzyme Gene in Vascular Smooth Muscle Cells

BACKGROUND: It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA. METHODS: RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard. RESULTS: 1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner. CONCLUSION: These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.