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Hyperglycemia in diabetes induces increased endothelin-1 (ET-1) production in the retina, kidney, and heart that may lead to hemodynamic impairment, permeability alteration, and increased extracellular matrix (ECM) protein production. Chronically elevated blood glucose levels may cause oxidative stress in these target tissues of diabetic complications. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme activated by DNA strand breaks due to oxidative stress. We investigated the role of PARP in regulating ET-1 expression and ET-1-induced abnormalities in the targets organs of diabetic complications. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. Once diabetes was established, half of the diabetic rats were randomly chosen to receive PARP inhibitor 3-aminobenzamide for 4 months. In a second set of experiments, PARP-/- mice and their controls were fed for 2 months with either a normal rodent diet or a 30% galactose diet to induce a normoinsulinemic hyperhexosemic state. Tissues harvested at the conclusion of both experiments were then subjected to real-time RT-PCR analysis for mRNA expression and immunohistochemical assessment of oxidative stress. In both experiments, the hyperhexosemic state upregulated expression of ET-1 mRNA in the retina, kidney, and heart. Furthermore, upregulation of ET-1-dependent ECM transcripts, such as fibronectin and extradomain B-containing fibronectin, was noted in all tissues. These tissues also demonstrated oxidative stress, as evidenced by the presence of nuclei positive for 8-hydroxy-2'-deoxyguanosine. In contrast, inhibition of PARP, either through a chemical means in the diabetic rats or by genetic manipulation in the galactose-fed animals, prevented both oxidative stress and hyperhexosemia-induced upregulation of these genes. These results suggest that, in diabetes, oxidative stress and PARP activation may produce their effects through ET-1. Hence, blockade of such pathways may constitute potential adjuvant treatment modalities in chronic diabetic complications.

To study the effect of notoginsenoside-Rg, on expression of BDNF mRNA (brain-derived neurotrophic factor messenger ribonucleic acid) in cerebrum cortex after MCAO/R (middle cerebral artery occlusion reperfusion) injury in rat by real-time quantitative polymerase chain reaction.36 SD male rats were randomly divided into MCAO/R model group, notogisenoside-Rg1 therapy group (100 mg/kg) and the positive medicine control group (nimodipine 1 mg/kg). The MCAO/R model were made by thread-occluded method. The four rats were randomly taken from each groups and were killed to be breaken out brain tissues as specimens after which were treated with medicine in 1,3, 5 days. Total RNA was isolated from cerebrum cortex. Specific oligonucleotide primers of BDNF mRNA gene fragments were amplificated by RT-PCR to construct recombinant plasmid and sequence. To dilute recombinant plasmid didploidly and a quantitative standard curve was completed. Taqman fluorogenic quantitative RT-PCR (FQ-PCR) was set up to detect the BDNF mRNA variety of cerebrum cortex.Compared with the model group and the postive control group, notogisenoside-Rg1 treated groups could obviously improve some nervous deficit symptoms in the cerebral ischemia and increase BDNF mRNA amount that in the cerebrum cortex at different period after rat MCAO/R injury.Notoginsenoside-Rg1 can promote to generating internal BDNF protein in brain by up-regulation the expression of BDNF mRNA amount in the cerebrum cortex. BDNF bind in TrkB, which can give rise to protective effects for ischemic neurons by generating corresponding domino effect molecules. Accordingly it can be as a therapy method in cerebral ischemia injury.

To investigate the retrograde amnesia changes within different injury levels of cerebral concussion in rats.A metallic pendulum striker device of brain injury was deployed to duplicate CC models of different injury levels within Sprague-Dawley (S-D) rats. The investigated animals were divided into two groups according to classification standard, that is, Pure Cerebral Concussion (PCC) group and Complicated Cerebral Concussion (CCC) group. One control group was used, and each group included 8 animals. The retrograde amnesia of each group was assessed by Morris Water Maze (MWM) Test from 3 days preinjury to 7 days postconcussion.Compared with the control group, the retrograde amnesia was detected within 3 days in PCC group, and 5 days in CCC group after injury. At the same time, the two groups both manifested space recognition deficit.The retrograde amnesia existed in both pure cerebral concussion group and complicated cerebral concussion. Furthermore, the lasting time of retrograde amnesia in animals correlates to the injury level of brain concussion.