ABSTRACT
Uremic toxins are harmful substances that accumulate in the body when the renal function declines in patients with chronic kidney disease (CKD). It is an important factor contributing to accelerated progression of CKD. There is no effective treatment for reducing uremic toxins. As an extensively used medicine for treatment of CKD in the clinic, Huangkui capsule is effective but the mechanism of its action remains unclear. This study investigated the effect of Huangkui on the accumulation of uremic toxins in CKD rats, with the discussion about its mechanism of action. UPLC-TQ/MS was used to detect the accumulation of uremic toxins in CKD rats after oral gavage with Huangkui. 16S rDNA sequencing technology was used to analyze the gut bacteria composition in rats. HPLC-FLD was used to detect the uremic toxins and their molecular precursors in feces. The effect and mechanism of Huangkui on the uremic toxin precursor in gut bacteria were studied by anaerobic culture system in vitro. All procedures were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine. The results showed that Huangkui (0.675 g·kg-1) could effectively inhibit the accumulation of uremic toxin indoxyl sulfate (IS) in CKD rats, with IS concentration in rat's plasma, liver and kidney decreased by 49.5%, 68.9% and 40.6%, respectively. Huangkui didn't affect the metabolic pathway of IS in host liver, didn't intervene the process of the IS precursor molecule indole conversion to IS. Instead, Huangkui significantly decreased the indole content in gut, with the indole in CKD rat's feces decreased by 46.4%, suggesting that the gut bacteria may be a target for intervene IS biosynthesis by Huangkui. Huangkui didn't affect the abundance of enterobacteriaceae bacteria (the main gut flora of indole synthesis) in CKD rats, suggesting that Huangkui didn't interfere with indole biosynthesis by directly affecting the abundance of indole synthesis related bacteria. Huangkui at 4 000, 400, 40, and 4 μg·mL-1 showed a dose-dependent inhibition of the indole production by gut bacteria in vitro. The bacteria tryptophan transport concentration decreased from 83.4 μmol·L-1 to 43.6 μmol·L-1 after co-incubated with Huangkui for 12 h, suggesting that Huangkui inhibited indole production of gut bacteria by interfering with tryptophan transportation. These results indicate that gut bacteria may be a potential target for alleviation of uremic toxin accumulation and for delaying CKD progression.
ABSTRACT
Based on standard carotid endarterectomy, we performed modified carotid endarterectomy in two cases of carotid artery stenosis by changing the direction of the carotid artery incision to avoid restenosis of the internal carotid artery without using a patch. The two patients recovered smoothly without any complications. Compared with eversion or patch endarterectomy, this modified carotid endarterectomy avoids restenosis of the carotid artery and shortens operation time.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the dynamic changes of dendritic cells (DCs) in the renal graft of rats within 72 h after renal transplantation.</p><p><b>METHODS</b>Using SD rats as the donors and Wistar rats as the recipients, renal transplantation was performed in 30 pairs of rats, with another 5 donor kidneys that were not transplanted serving as the sham operation group. The transplanted kidneys were harvested at 1, 6, 12, 24, 48 and 72 h after recovery of blood circulation, paraffin-embedded and sectioned ,followed by HE staining and immunohistochemical staining for S-100 protein for DC identification. The pathological changes and the DC density per glomerulus in the renal graft were observed with optical microscope.</p><p><b>RESULTS</b>No signs of acute rejection were found in these sections. Few DCs were observed in the sham operation group and in the renal graft 1 h after transplantation. The number of DCs in the renal graft increased with time and reached the maximum 24 h after transplantation followed by gradual decrease.</p><p><b>CONCLUSIONS</b>Within 72 h after renal transplantation, the number of DCs in the graft varies following a curve with a single peak. Increased DC density in the graft may result from recipient DC migration into the graft, and accordingly, decreased recipient DC migration results in decrease of DC density in the graft. The pattern of DC number variation in the graft can be helpful to further improve the therapy against graft rejection.</p>