Electroacupuncture inhibits PDK1/Akt/HCN4 pathway to improve neurogenic urinary retention in rats. / 电针通过抑制PDK1/Akt/HCN4é€šè·¯æ”¹å–„å¤§é¼ ç¥žç»æºæ€§å°¿æ½´ç•™.

OBJECTIVES: To observe the therapeutic effect of electroacupuncture (EA) on neurogenic urinary retention rats, so as to explore the underlying mechanism of EA in treating neurogenic urinary retention by focusing on 3-phosphoinositide-dependent protein kinase 1 (PDK1)/protein kinase B (Akt)/hyperpolarization activated cyclic nucleotide-gated cation channel 4 (HCN4) pathway. METHODS: Female SD rats were randomly divided into sham operation, model, EA, PDK1 inhibitor, HCN4 blocker and EA + HCN4 blocker groups, with 20 rats in each group. The model of sacral spinal cord injury was established by modified Hassan Shaker spinal cord transection method. EA (2 Hz/15 Hz, 0.5 mA) was applied to "Zhongji" (CV3) and "Zhongliao" (BL33) for 20 min, once daily for 10 days. Rats of the PDK1 inhibitor group received intraperitoneal injection of OSU-03012 (20 mg/kg), and rats of the HCN4 blocker group received intraperitoneal injection of ivabradine (10 mg/kg), both once every other day for 10 days. The urodynamic indexes of rats were detected by multi-channel physiological recorder；muscle strip test was used to detect detrusor excitability；the morphological changes of bladder were observed by HE staining. Immunofluorescence double staining was used to detect the co-expression of HCN4 and C-Kit, a specific marker of interstitial cells of Cajal in bladder. Western blot was used to detect the expression of PDK1/Akt/HCN4 pathway proteins in bladder tissue and heat shock protein 27 (HSP27), a protein related to bladder contraction function. RESULTS: Compared with the sham operation group, the rats in the model group showed urinary dysfunction, decreased leak point pressure, isolated detrusor spontaneous contraction frequency, fluorescence intensity of C-Kit positive cells, HCN4+/C-Kit+ co-expression, HCN4 and p-HSP27/HSP27 protein expression in bladder tissue (P<0.05), and increased maximum bladder capacity and comp-liance, minimum tension during contraction of isolated detrusor, PDK1 and p-Akt/Akt protein expression in bladder tissue (P<0.05). Meanwhile, the above index were all reversed after EA and PDK1 inhibitor intervention (P<0.05). In comparison with the EA group, the rats had severe urinary dysfunction, the urine leakage point pressure, spontaneous contraction frequency, fluorescence intensity of C-Kit positive cells, the co-expression of HCN4+/C-Kit+, and the protein expression of HCN4 and p-HSP27/HSP27 were decreased (P<0.05), the maximum bladder capacity and compliance, the minimum tension during contraction of isolated detrusor, and the protein expression of PDK1 and p-Akt/Akt in bladder tissue were increased (P<0.05) in both HCN4 blocker and EA+HCN4 blocker groups. HE staining showed exfoliated bladder epithelium and disordered layers, vacuolization of bladder wall cells, with infiltration of neutrophils in mucosal and muscular layers in the model group, which were relatively milder in the EA and PDK1 inhibitor groups, but worse in the HCN4 blocker and EA + HCN4 blocker groups. CONCLUSIONS: EA can improve the urinary dysfunction in rats with neurogenic urinary retention, which may be related to its effect in inhibiting the activation of PDK1/Akt pathway, promo-ting HCN4-mediated detrusor excitatory contraction and urinary electrical signal activation.

Targeted puncture of left branch of intrahepatic portal vein in transjugular intrahepatic portosystemic shunt to reduce hepatic encephalopathy.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is currently used for the treatment of complications of portal hypertension. The incidence of hepatic encephalopathy (HE) remains a problem in TIPS placement. It has been reported that the right branch mainly receives superior mesenteric venous blood while the left branch mainly receives blood from the splenic vein. We hypothesized that targeted puncture of the left portal vein would divert the non-nutritive blood from the splenic vein into the TIPS shunt; therefore, targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE. AIM: To evaluate the influence of targeted puncture of left branch of portal vein in TIPS on HE. METHODS: A retrospective analysis of 1244 patients with portal-hypertension-related complications of refractory ascites or variceal bleeding who underwent TIPS from January 2000 to January 2013 was performed. Patients were divided into group A (targeting left branch of portal vein, n = 937) and group B (targeting right branch of portal vein, n = 307). TIPS-related HE and clinical outcomes were analyzed. RESULTS: The symptoms of ascites and variceal bleeding disappeared within a short time. By the endpoint of follow-up, recurrent bleeding and ascites did not differ significantly between groups A and B (P = 0.278, P = 0.561, respectively). Incidence of HE differed significantly between groups A and B at 1 mo (14.94% vs 36.80%, χ 2 = 4.839, P = 0.028), 3 mo (12.48% vs 34.20%, χ 2 = 5.054, P = 0.025), 6 mo (10.03% vs 32.24%, χ 2 = 6.560, P = 0.010), 9 mo (9.17% vs 31.27%, χ 2 = 5.357, P = 0.021), and 12 mo (8.21% vs 28.01, χ 2 = 3.848, P = 0.051). There were no significant differences between groups A and B at 3 years (6.61% vs 7.16%, χ 2 = 1.204, P = 0.272) and 5 years (5.01% vs 6.18%, χ 2 = 0.072, P = 0.562). The total survival rate did not differ between groups A and B (χ 2 = 0.226, P = 0.634, log-rank test). CONCLUSION: Targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE but has no direct influence on prognosis of portal-hypertension-related complications.