Protective Effect of Different Medicinal Parts of Nandina domestica on Arsenic Trioxide Hepatotoxicity and Hephrotoxicity / 中国实验方剂学杂志

Objective::To compare the effect of different medicinal parts of Nandina domestica in reducing toxicity of anti-tumor drug arsenic trioxide, so as to provide the scientific basis for its further development and application. Method::Chronic arsenic trioxide poisoning model was used in this paper. Totally 56 SD rats were randomly divided into normal group, model group (arsenolite 40 mg·kg-1), sodium 2, 3-dimercapto-1-propanesulfonate group (sodium 2, 3-dimercapto-1-propanesulfonate 25 mg·kg-1+ arsenolite 40 mg·kg-1), Nandinae Radix group (Nandinae Radix 20 g·kg-1+ arsenolite 40 mg·kg-1), Nandinae Caulis group (Nandinae Caulis 20 mg·kg-1+ arsenolite 40 mg·kg-1), Nandinae Folium group (Nandinae Folium 20 g·kg-1+ arsenolite 40 mg·kg-1), and Nandinae Fructus group (Nandinae Fructus 20 g·kg-1+ arsenolite 40 mg·kg-1). The intragastric administration lasted for 10 days. After the last administration, urine was collected within 24 hours, serum, kidney and liver tissue samples were collected after operation, and serum creatinine (SCr) and urine creatinine (UCr) levels were measured, in order to calculate endogenous creatinine clearance rate (CCr). At the same time, the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in liver and kidney of rats in each group were detected. Some kidneys and livers were fixed with formaldehyde, and the histopathological changes were observed under microscope after hematoxylin-eosin staining. Result::Compared with the model group, the rats in combination group of Nandinae Radix, Nandinae Caulis, Nandinae Fructus have a heavier body mass (P<0.01), the kidney coefficient was lower (P<0.01), the levels of UCr and CCr were significantly increased (P<0.01), the content of MDA in renal tissue was decreased significantly (P < 0.01), the level of MDA in liver tissue was decreased (P < 0.05), whereas the activities of SOD and CAT were significantly increased (P<0.01), the pathological damage of liver and kidney was alleviated. There was no significant difference in the activity of SOD in the liver between the Nandinae Folium combination group and the model group, but the changes of the other indexes were consistent with those of the above three groups. Conclusion::Nandinae Radix, Nandinae Caulis, Nandinae Fructus have significant protective effects on liver and kidney toxicity induced by arsenic trioxide oxidative stress, and Nandinae Folium was the least effective among them.

Immunohistochemical study of Cx43 dephosphorylation in human left ventricular myocardium suffered by acute ischemia / 法医学杂志

OBJECTIVE@#This study was performed to detect the phosphorylation state of Cx43 in human left ventricular myocardium among sudden deaths caused by acute myocardial ischemia (AMI) especially sudden coronary death (SCD) and control groups. And then evaluate the significance of these findings in diagnosing the early pathological changes of acute myocardial ischemia.@*METHODS@#Immunohistochemistry (IHC) SP techniques were adopted to detect the phosphorylation state of Cx43 in the left ventricular myocardium samples of 45 deceased, which classified as group I--SCD, group II & III (other two groups of AMI) and Group IV & V (two control groups, sudden death caused by lethal acute cranio-cerebral injury or pathologic intracranial hemorrhage). In addition, we selected anti-Pan-Cadherin (construction protein of adherent junctions on the intercalated disc) and PHA-E+L/Bio, to detect the integration of myocardial mechanical coupling and membranes (applying affinityhistochemistry, AHC) respectively.@*RESULTS@#(1) Phosphorylated Cx43 positive staining was almost invisible in Group I, II and III or scattered in sarcoplasm in few samples; but it was assembling at the IDs clearly in group IV and V. (2) Strongly positive staining of Pan-Cadherin could be observed at the IDs and (3) integrated myocardial membranes were found in all samples.@*CONCLUSION@#These findings suggested that compared with the control groups, the integration of myocardial mechanical coupling and membranes did not alter in AMI. But Cx43, the key protein of electrical coupling on myocardial gap junctions, occurred dephosphorylation remarkably in AMI. Thus applying IHC techniques to detect the Cx43 dephosphorylation in human left ventricular myocardium maybe useful to recognize the onset of arrhythmia in AMI, especially in SCD whose myocardium without apparent morphological changes.

Gap junctions, connexins and sudden death caused by coronary heart disease / 法医学杂志

Gap junctions construct hydrophilic trans-membrane channels which adjust the intercellular communication of chemistry and electricity. In the heart, individual cardiac myocytes are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the myocardium, ensuring their synchronous contraction. In recent years, some researchers have found that connexins, the protein molecules of gap junction channels, are reduced in number or redistributed from intercalated disks (ID) to lateral cell borders in a variety of cardiac disease, especially in ischemic heart disease. The gap junction remodeling is considered to be arrhythmogenic. These findings will lead us to a new realm in the diagnostic of sudden death caused by coronary heart disease.