The Study Of The Yang-warming And Fluid Retention-resolving Therapy On Expression Of The Renal Medulla Differences Genes And Aquaporin In Lung And Kidney About Chronic Heart Failure Of Rat

Objective:To observe the Linggui Zhugan decoction and Tingli Dazao Xiefei decoction add to together, as an object study by Adriamycin(Adr) induce to rat Congestive heart failure(CHF), Aquaporin(AQP) as an effector molecule action target to therapy retained fluid, to explore the molecule mechanism of eliminating retained fluid by yang-warming and fluid retention-resolving therapy.Methods:Using the digitally random methods to divides the adult Wistar rats into blank control group (K) and A group, the animal in A group was intraperitoneal injection by Adriamycin induce to rat Congestive heart failure model. After modeling divides the adult Wistar rats into three groups, the yang-warming and fluid retention-resolving therapy group (W), wiping off the cassia twig fluid retention-resolving group(Q) and model control group(M). ①According to equivalent dose about 12g/kg·d give the W group yang-warming and fluid retention-resolving decoction by gavage once daily for 4 weeks. ②According to equivalent dose about 10g/kg·d give the Q group wiping off the cassia twig fluid retention-resolving decoction by gavage once daily for 4 weeks. ③The blank control group and model control group feeding at the same condition but give nothing medicine. After the experiment, the hemodynamics in all rats was measured. Testing the content about ANP、BNP and Ang Ⅱ, the content about Aquaporin2 (AQP2) in kidney and Aquaporin5 (AQP5) in lung tissue, and the content of cAMP、PKAand PKC in lung and kidney tissue. Observing the morphology change about ventricular muscle. Using gene chip technology detecting the gene expression profile in medulla kidney, screen out the differential expression gene, annotation by gene ontology and analysis by pathway.Results;1.The Systolic arterial pressure(SAP)、Diastolic arterial pressure(DAP)、Mean arterial pressure(MAP)and the left ventricle increased rate of maximum in model control group are all decreased significantly control with the blank control group (P< 0.05 or P<0.01). The yang-warming and fluid retention-resolving and wiping off the cassia twig fluid retention-resolving decoction can increased the DAP and MAP control with the model control group (P<0.05 or P<0.01),but the LVEDP is decreased significantly(P<0.01)2.The content of ANP、BNP and AngⅡ in model control group are all increased control with the blank control group. The yang-warming and fluid retention-resolving and wiping off the cassia twig fluid retention-resolving decoction can decreased the content of BNP and Ang II but they are higher than the blank control group (P<0.05 or P< 0.01)3.The content about AQP2 in kidney and AQP5 in lung tissue are decreased significant in model control group comparing with the blank control group (P<0.01). The yang-warming and fluid retention-resolving and wiping off the cassia twig fluid retention-resolving decoction can increased the AQP2 in kidney and AQP5 in lung tissue comparing with the model control group (P<0.05 or P<0.01)4.The differential expression gene in model control group comparing with the blank control group involve much biological process, the signal pathway include myocardial contraction, dilated cardiomyopathy, hypertrophic cardiomyopathy(HCM). Ryr2 gene is the main differential gene.5.The differential expression gene in the yang-warming and fluid retention-resolving group comparing with the model control group include MAPK signal transduction pathway, NOD receptor-like receptor pathway. The differential expression gene in the wiping off the cassia twig fluid retention-resolving group comparing with the blank control group include adipose cytokines pathway, hypertrophic cardiomyopathy.Conclusion:1.The CHF can made by Adr, Cause rat hemodynamic and cardiac endocrine abnormalities.2.The yang-warming and fluid retention-resolving decoction can increased the DAP in CHF model rat, decreased the LVEDP, improve the function of heart by CHF rat.3.The yang-warming and fluid retention-resolving decoction can increased the content of ANP、BNP and Ang II in plasma about CHF rat significantly, improve the heart of internal secretion function about CHF rat,4.The yang-warming and fluid retention-resolving can increased the expression of AQP2 in kidney and AQP5 in lung about rat in CHF model, it may be possible molecule mechanism to regulate retained fluid by govern regulation of the waterways and the kidney controlling water metabolism.5.There are no consistency about the expression of AQP2 in kidney and AQP5 in lung compared with the expression of cAMP、PKA and PKC in every group. There are no correlation in the yang-warming and fluid retention-resolving therapy group compared with model control group, wiping off the cassia twig fluid retention-resolving group compared with model control group in cAMP-PKA signal pathway by differential gene. So, the cAMP-PKA signal pathway may be not the key factor to regulate and control AQP2 in kidney and AQP5 in lung.6.This is the first study from the renal medulla of CHF rats were found in the abnormal expression of Ryr2 gene, suggesting that the kidney in heart failure myocardial excitation contraction coupling plays an important regulatory role.7.The yang-warming and fluid retention-resolving decoction can get through the MAPK signal transduction pathway and the NOD receptor-like receptor pathway to restrain the apoptosis about the kidney to treat the CHF.